Materiały źródłowe

• #1 Endometrial Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK525981/

  Endometrial cancer is a malignancy originating within the epithelial lining of the uterus. […] The condition has historically been classified into type 1 and type 2 endometrial cancer based on histological characteristics. However, results from recent studies have begun classifying endometrial cancers according to a current molecular subgrouping system. Type 1 cancers are more common, with 80% of all endometrial cancers of endometrioid origin. Type 2 endometrial cancers are primarily of serous or clear cell origin. The most significant risk factors associated with endometrial cancer development include those that increase long-term exposure to unopposed estrogen (eg, obesity and exogenous estrogen). […] Present consensus holds that the pathogenesis of most low-grade endometrial carcinomas begins with uninterrupted endometrial proliferation, hormonally stimulated by endogenous or exogenous estrogen unopposed by progesterone or progestins, progressing through states of simple to complex forms of endometrial hyperplasia.

• #2 Endometrial Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9421940/

  Endometrial cancer (EC) is often a hormone-sensitive disease thought to commonly arise in the context of excessive estrogenic stimulation of the endometrial lining of the uterus. This estrogenic stimulation leads to mitogenic stimulation, and ultimately, malignant transformation of the endometrial glandular epithelium, and accounts for the development of the more common and lower grade endometrioid ECs. Risk factors for hyperestrogenism include obesity, hormone therapy (such as tamoxifen), ovarian cortical hyperplasia (hyperthecosis), polycystic ovarian syndrome, and hormone-producing tumors. […] Endometrioid ECs develop through malignant transformation of the precursor lesions atypical endometrial hyperplasia (AEH) also known as endometrial intraepithelial neoplasia. AEH often contains somatic PTEN mutations; loss of PTEN is necessary for the development of AEH but is insufficient for progression to invasive carcinoma. ARID1A has a critical role in the transition of precursor AEH lesions to invasive endometrioid carcinomas, and inactivation of TGFB also contributes to the progression of AEH to invasive carcinoma.

• #3 Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy

  https://www.mdpi.com/2072-6694/16/11/2027

  Endometrial cancer is a complex disease with multiple risk factors, distinct histological subtypes, and a variety of available therapeutic options. The disease’s pathogenesis involves several molecular mechanisms, such as genetic mutations, defects in the DNA mismatch repair (MMR) pathway, hormonal signaling pathway imbalances, epigenetic changes, and disturbances in angiogenesis. […] This review focuses on the molecular mechanisms involved in the pathogenesis of endometrial cancers, such as genetic mutations, defects in the DNA mismatch repair pathway, epigenetic changes, or dysregulation in angiogenic or hormonal signaling pathways. […] The pathogenesis of endometrial cancer implies complex molecular mechanisms responsible for the appearance of genetic mutations, the activation of oncogenes accompanied by the inactivation of tumor suppressor genes, defects in the DNA mismatch repair (MMR) pathway, imbalance in hormonal signaling pathways, epigenetic modifications, or disorders in angiogenesis.

• #4 Endometrial Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9421940/

  The less common and more aggressive uterine serous carcinomas and the rarer uterine clear cell carcinomas are likely manifestations of increased genotoxic stress that is directly mediated through mutational and epigenetic activation of endometrial precursor cells. These EC subtypes often arise from precursor lesions such as serous endometrial intraepithelial carcinoma (SEIC). SEIC precursor lesions are thought to contain initiating TP53 mutations, as evidenced by abnormal immunohistochemistry staining of p53 and some reports of identifiable somatic TP53 mutations in SEIC precursor lesions and invasive disease. […] Four molecular subgroup of EC defined by mutation burden and copy number alterations have been categorized in a study of 373 cases of EC by the TCGA. Most ECs have near diploid tumors or focal copy number alterations. Moreover, the mutational burden of most ECs reflects that of most solid tumors, with ~2-3 somatic mutations per megabase sequenced.

• #5 Pathogenesis and Treatments of Endometrial Carcinoma

  https://www.imrpress.com/journal/CEOG/50/11/10.31083/j.ceog5011229/htm

  Endometrial cancer (EC) is a common gynecological malignancy with an estimated incidence of more than 65,000 new cases in the United States in 2022. Considering the increase in incidence over the last decade and the continuing high mortality, it is crucial to better understand the causes and the treatment of this malignancy. The essential prerequisite to understand EC pathogenesis is an effective classification of ECs, to better determine oncological outcomes. The year 2013 marks a turning point, when the Cancer Genome Atlas (TCGA) Research Network surpassed the limits of dualistic EC classification by incorporating molecular analysis of EC using the most modern array and sequencing-based technologies. Consequently, ECs were re-classified and divided into the following four classes with individual recurrence risk and progression-free survival (PFS): DNA polymerase epsilon (POLE), microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR), copy-number-low/TP53-wild-type (CNL), and copy-number-high/TP53-mutant (CNH/p53abn). Since TCGA classification had some practical limits for immediate clinical application, a new algorithm whose acronym is ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) was adopted as determined by the Institute of Medicine’s guidelines. Numerous steps are included in this model that has been widely validated. Moreover, the available data confirmed the applicability of this model to the final and diagnostic specimens (i.e., hysterectomy, curettages or endometrial biopsies). These innovative steps had been applied in the last European Society for Radiotherapy and Oncology (ESTRO)—European Society of Gynaecological Oncology (ESGO)—European Society of Pathology (ESP) 2020 Guidelines for the approach to women with EC with the objective to use specific profiling to determine the most suitable and personalized adjuvant approaches.

• #6 Endometrial Cancer – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/gynecologic-tumors/endometrial-cancer

  There are 4 distinct molecular subtypes of endometrioid endometrial carcinomas: POLE ultramutated (POLEmut): Characterized by pathogenic mutations in the exo nuclease domain of DNA polymerase-, resulting in an ultra-high tumor mutational burden and a good prognosis; Mismatch repair-deficient (MMRd): Has loss of mismatch repair proteins, resulting in microsatellite instability and an intermediate prognosis; No specific molecular profile (NSMP): Has no single identifying molecular feature and tumor stage- and grade-dependent outcomes and an intermediate prognosis; p53-mutant: Has a low tumor mutational burden and high somatic copy-number alterations resulting in a poor prognosis. […] Determining the molecular subtype, if feasible, adds valuable information to the standard clinicopathological risk factors to classify patients with endometrial cancer into risk groups, predict prognosis, and guide treatment recommendations.

• #7 Endometrial Cancer Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq

  PTEN variants are more common in type 1 endometrial cancers; TP53 and HER2/neu overexpression are more common in type 2 endometrial cancers, although some overlap exists. […] The Cancer Genome Atlas’s full genetic display of hundreds of endometrial cancers identified four subtypes to further characterize endometrial cancers: POLE ultramutated. This subtype has clinical significance, and adjuvant therapies are avoided. […] Microsatellite instability hypermutated. […] Copy number low. […] Copy number high. […] These categories can be used to stratify patients into low- and high-risk prognostic categories.

• #8 Endometrial Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9421940/

  The identification of the molecular subgroups has rapidly changed the way ECs are stratified and treated. Several groups have taken these initial findings from TCGA and extrapolated them for better application to clinical practice. One approach – known as ProMisE (proactive molecular risk classifier for EC) – uses IHC to identify mismatch repair proteins and p53, and sequences the POLE exonuclease domain. ProMisE has identified four molecular subtypes of EC that are analogous but not identical to the four genomic subtypes described in TCGA study: MMRd, DNA POLE (corresponding to the ultramutated (POLE mutated) subtype), p53abn (which demonstrates aberrant p53 immunohistochemical staining and corresponds to the CNH subtype) and p53wt (which corresponds to the CNL subtype). Cases lacking enough information to classify are designated NSMP.

• #9 Endometrial Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK525981/

  Endometrial cancer is a malignancy originating within the epithelial lining of the uterus. […] The condition has historically been classified into type 1 and type 2 endometrial cancer based on histological characteristics. However, results from recent studies have begun classifying endometrial cancers according to a current molecular subgrouping system. Type 1 cancers are more common, with 80% of all endometrial cancers of endometrioid origin. Type 2 endometrial cancers are primarily of serous or clear cell origin. The most significant risk factors associated with endometrial cancer development include those that increase long-term exposure to unopposed estrogen (eg, obesity and exogenous estrogen). […] Present consensus holds that the pathogenesis of most low-grade endometrial carcinomas begins with uninterrupted endometrial proliferation, hormonally stimulated by endogenous or exogenous estrogen unopposed by progesterone or progestins, progressing through states of simple to complex forms of endometrial hyperplasia.

• #10 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  Endometrial cancer is the most common gynecologic malignancy in developed countries, and the incidence is rising in premenopausal females. […] Estrogen unopposed by progesterone is considered to be the main driving factor in the pathogenesis of EC. […] Hyperestrogenic states, or increased estrogen exposure, have been proven to be the main driver in the development of Type I EC. […] The unopposed estrogen hypothesis, first described by Key et al. (1988), is a widely accepted theory stating that women with high circulating levels of endogenous estrogen unopposed by progesterone run an increased risk of developing EC. […] This states that estrogen unopposed by sufficient progesterone leads to the unregulated mitogenic effects of estrogen, leading to increased endometrial proliferation during the follicular phase, and increased EC risk among young women with increased endogenous or exogenous estrogen levels.

• #11 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  Endometrial cancer is the most common gynecologic malignancy in developed countries, and the incidence is rising in premenopausal females. […] Estrogen unopposed by progesterone is considered to be the main driving factor in the pathogenesis of EC. […] Hyperestrogenic states, or increased estrogen exposure, have been proven to be the main driver in the development of Type I EC. […] The unopposed estrogen hypothesis, first described by Key et al. (1988), is a widely accepted theory stating that women with high circulating levels of endogenous estrogen unopposed by progesterone run an increased risk of developing EC. […] This states that estrogen unopposed by sufficient progesterone leads to the unregulated mitogenic effects of estrogen, leading to increased endometrial proliferation during the follicular phase, and increased EC risk among young women with increased endogenous or exogenous estrogen levels.

• #12 Endometrial cancer: Pathophysiology, diagnosis and management – IJCAAP

  https://www.ijcap.in/html-article/18885

  Long-term oestrogen exposure without progestin opposition is a significant predictor for type I EC. Both endogenous and exogenous oestrogen exposure are possible. Hormone replacement therapy is one form of exogenous oestrogen exposure. Obesity, estrogen-producing tumors, and persistent anovulation are all risk factors for endogenous oestrogen exposure. […] Obesity is the primary risk factor for endometrial hyperplasia developing into malignant cancer. Obesity results in excessive peripheral conversion of androgens to estrone in adipose cells; this extra oestrogen promotes endometrial lining growth and frequently results in carcinogenesis. Moreover, prolonged anovulation is more prevalent in obese premenopausal women, which is also a major contributing factor for overexposure of estrogen.

• #13 Endometrial Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK525981/

  Endometrial cancer is a malignancy originating within the epithelial lining of the uterus. […] The condition has historically been classified into type 1 and type 2 endometrial cancer based on histological characteristics. However, results from recent studies have begun classifying endometrial cancers according to a current molecular subgrouping system. Type 1 cancers are more common, with 80% of all endometrial cancers of endometrioid origin. Type 2 endometrial cancers are primarily of serous or clear cell origin. The most significant risk factors associated with endometrial cancer development include those that increase long-term exposure to unopposed estrogen (eg, obesity and exogenous estrogen). […] Present consensus holds that the pathogenesis of most low-grade endometrial carcinomas begins with uninterrupted endometrial proliferation, hormonally stimulated by endogenous or exogenous estrogen unopposed by progesterone or progestins, progressing through states of simple to complex forms of endometrial hyperplasia.

• #14 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  Longer duration of unopposed estrogen exposure causing excess proliferation increases the probability of mutations, specifically in proto-oncogenes and tumor suppressor genes. […] Studies have consistently demonstrated that premenopausal women with a hyperestrogenic state are at an increased risk of developing EC. […] Obesity is established as a leading cause of Type I EC throughout the lifespan. […] Higher BMIs have been associated with lower-grade cancers. […] For example, Crosbie et al. (2012) found that WHO class III obesity (BMI > 40 kg/m²) was associated with a more significant proportion of isolated endometrial involvement and well-differentiated carcinomas when compared to normal-weight individuals. […] The Million Women Study found that the relative risk of developing EC was 1.87 for every 5-kg/m² increase in BMI in postmenopausal women.

• #15 Pathology Outlines – Endometrial hyperplasia

  https://www.pathologyoutlines.com/topic/uterusendometrialhyperplasiageneral.html

  Proliferation of endometrial glands with a resulting increase in gland to stroma ratio […] Atypical hyperplasia / endometrioid intraepithelial neoplasia (AH / EIN) is considered a premalignant condition […] Increased risk of both progression to and simultaneous endometrial endometrioid adenocarcinoma […] Estrogen driven precursor lesion to endometrial endometrioid adenocarcinoma […] Increased endogenous or exogenous estrogen, unopposed by progesterone […] Initially, estrogen has mitogenic effect on both endometrial glands and stroma […] Chronic estrogenic stimulation without progesterone affects glands to a greater extent → glandular overgrowth (hyperplasia) […] AH / EIN associated with […] Progression to endometrial endometrioid adenocarcinoma in up to 28% of cases without hysterectomy after 20 year followup

• #16 Endometrial cancer pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Endometrial_cancer_pathophysiology

  Development of endometrial cancer is the result of multiple genetic mutations. Genes involved in the pathogenesis of endometrial cancer include TP53, KRAS, and PTEN. The pathophysiology of endometrial cancer depends on the histological subtype. […] Endometrial cancer forms when there are errors in normal endometrial cell growth. […] Development of an endometrial hyperplasia (overgrowth of endometrial cells) is a significant risk factor because hyperplasia can and often do develop into adenocarcinoma, though cancer can develop without the presence of a hyperplasia. Within ten years, 830% of atypical endometrial hyperplasias develop into cancer, whereas 13% of non-atypical hyperplasias do so. […] Mutations in the KRAS gene can cause endometrial hyperplasia and therefore type I endometrial cancer. Endometrial hyperplasia typically occurs after the age of 40. Endometrial glandular dysplasia occurs with an overexpression of TP53, and develops into a serous carcinoma (type II endometrial cancer).

• #17 Endometrial Cancer | AAFP

  https://www.aafp.org/pubs/afp/issues/2009/1115/p1075.html

  Endometrial cancer is characterized by neoplasia of the glandular elements of the endometrium and is classified as type I or type II based on histologic properties. Type I, also called the endometrioid type because of its histologic similarity to the endometrium, accounts for more than 75 percent of cases. Most type I tumors occur in the setting of unopposed estrogen stimulation, leading to endometrial hyperplasia. Previously, hyperplasia was thought to progress along a continuum that led to endometrial cancer. Recent studies show that although some hyperplasias do progress to adenocarcinoma, others coexist with endometrial cancer. The probability of endometrial hyperplasia progressing to adenocarcinoma is greater in patients who have a higher degree of cytologic atypia, as described by the World Health Organization classification system. Simple hyperplasia without cellular atypia has a 1 percent probability of progressing to carcinoma if left untreated; with cellular atypia, the probability is 8 percent. Complex hyperplasia without cellular atypia has a 3 percent probability of progressing; with cellular atypia, the probability is 29 percent.

• #18 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  Endometrial cancer is the most common gynecologic malignancy in developed countries, and the incidence is rising in premenopausal females. […] Estrogen unopposed by progesterone is considered to be the main driving factor in the pathogenesis of EC. […] Hyperestrogenic states, or increased estrogen exposure, have been proven to be the main driver in the development of Type I EC. […] The unopposed estrogen hypothesis, first described by Key et al. (1988), is a widely accepted theory stating that women with high circulating levels of endogenous estrogen unopposed by progesterone run an increased risk of developing EC. […] This states that estrogen unopposed by sufficient progesterone leads to the unregulated mitogenic effects of estrogen, leading to increased endometrial proliferation during the follicular phase, and increased EC risk among young women with increased endogenous or exogenous estrogen levels.

• #19 Endometrial cancer: Pathophysiology, diagnosis and management – IJCAAP

  https://www.ijcap.in/html-article/18885

  Long-term oestrogen exposure without progestin opposition is a significant predictor for type I EC. Both endogenous and exogenous oestrogen exposure are possible. Hormone replacement therapy is one form of exogenous oestrogen exposure. Obesity, estrogen-producing tumors, and persistent anovulation are all risk factors for endogenous oestrogen exposure. […] Obesity is the primary risk factor for endometrial hyperplasia developing into malignant cancer. Obesity results in excessive peripheral conversion of androgens to estrone in adipose cells; this extra oestrogen promotes endometrial lining growth and frequently results in carcinogenesis. Moreover, prolonged anovulation is more prevalent in obese premenopausal women, which is also a major contributing factor for overexposure of estrogen.

• #20 Endometrial Carcinoma: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/254083-overview

  Endometrial cancer (also referred to as corpus uterine cancer or corpus cancer) is the most common female genital cancer in the developed world, with adenocarcinoma of the endometrium the most common type. […] Multiple epidemiological risk factors have been identified in patients who have adenocarcinoma of the endometrium. […] Unopposed estrogen, either as replacement therapy or endogenously produced (eg, granulosa cell tumor, polycystic ovarian disease), increases the risk of endometrial cancer. […] Obesity is known to increase endogenous estrogen because the presence of fat appears to be responsible for the conversion of androstenedione to estrogen compounds at a much higher rate than if fat is not present. […] Anovulation, which may be secondary to unopposed estrogen, also appears to contribute to this situation.

• #21 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  Longer duration of unopposed estrogen exposure causing excess proliferation increases the probability of mutations, specifically in proto-oncogenes and tumor suppressor genes. […] Studies have consistently demonstrated that premenopausal women with a hyperestrogenic state are at an increased risk of developing EC. […] Obesity is established as a leading cause of Type I EC throughout the lifespan. […] Higher BMIs have been associated with lower-grade cancers. […] For example, Crosbie et al. (2012) found that WHO class III obesity (BMI > 40 kg/m²) was associated with a more significant proportion of isolated endometrial involvement and well-differentiated carcinomas when compared to normal-weight individuals. […] The Million Women Study found that the relative risk of developing EC was 1.87 for every 5-kg/m² increase in BMI in postmenopausal women.

• #22 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  A systematic review and meta-analysis by Renehan et al. (2008) demonstrated that, in premenopausal women, the risk of developing EC increases 1.59-fold with each 5 kg/m² increase in BMI at a BMI of 28 and above. […] There is a rising rate of obesity in developed nations, which is a likely cause of the increase in the incidence of endometrial carcinoma in the premenopausal population. […] Chronic hyperinsulinemia is tumorigenic in estrogen-sensitive tissues. […] The insulin-driven reduction of sex-hormone-binding globulin (SHBG) increases estrogen availability. […] Increased estradiol will stimulate endometrial cell proliferation and inhibit apoptosis, and it has been shown to stimulate insulin-like growth factor-I (IGF-I) in endometrial tissue. […] Polycystic Ovarian Syndrome (PCOS) is relatively common, affecting up to 8% of women, and polycystic ovaries (PCO) without the clinical diagnosis of PCOS affect up to 20% of women.

• #23 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  A systematic review and meta-analysis by Renehan et al. (2008) demonstrated that, in premenopausal women, the risk of developing EC increases 1.59-fold with each 5 kg/m² increase in BMI at a BMI of 28 and above. […] There is a rising rate of obesity in developed nations, which is a likely cause of the increase in the incidence of endometrial carcinoma in the premenopausal population. […] Chronic hyperinsulinemia is tumorigenic in estrogen-sensitive tissues. […] The insulin-driven reduction of sex-hormone-binding globulin (SHBG) increases estrogen availability. […] Increased estradiol will stimulate endometrial cell proliferation and inhibit apoptosis, and it has been shown to stimulate insulin-like growth factor-I (IGF-I) in endometrial tissue. […] Polycystic Ovarian Syndrome (PCOS) is relatively common, affecting up to 8% of women, and polycystic ovaries (PCO) without the clinical diagnosis of PCOS affect up to 20% of women.

• #24 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  The condition is characterized by oligo- or anovulation, signs of androgen excess, and an excess of small ovarian cysts. […] Chronic anovulation leads to chronic estrogen exposure which, as stated above, can lead to endometrial hyperplasia and neoplasia. […] The association between PCOS and EC was described as early as 1949 and is based on several factors. […] Early treatment of PCOS may reduce the risk of the development of endometrial cancer by targeting BMI and insulin resistance. […] There is evidence that the incidence of EC in the premenopausal population continues to rise. […] The most commonly reported risk factors are obesity, nulliparity, longer duration of menses (earlier age at menarche or late age of menopause), a history of anovulatory cycles, PCOS, diabetes mellitus, and/or unopposed estrogen therapy.

• #25 Endometrial cancer: Pathophysiology, diagnosis and management – IJCAAP

  https://www.ijcap.in/html-article/18885

  Genetic mutations associated to molecular signalling pathways plays important role in the aetiology of EC. This molecular pathways are hampered by circumstances including suppression of cell proliferation, apoptosis, elevation of telomere reverse transcription, and DNA synthesis abnormalities. Genetic Alteration in the phosphate and tensin homolog (PTEN), Catenin beta-1 (CTNNB1), Kirsten rat sarcoma (KRAS) viral oncogene homolog, AT-rich interaction domain 1A (ARID1A),and mismatch repair (MMR) molecular pathways have a substantial impact on ECs. […] Hyperinsulinism is linked to diabetes mellitus or PCOS and plays a significant role in the development of cancer, as it amplifies mitotic activity in the glands and stroma by boosting IGF-1 activity. Excess insulin increases blood free testosterone levels by reducing the formation of the liver sex hormone-binding globulin (SHBG), enhances the production of androgens driven by LH and IGF-I, and increases serum IGF-I bioactivity by suppressing the development of IGF-binding proteins. Women with EC also have insulin binding sites expressed in their endometrial stroma. It follows that excessive insulin signalling can cause endometrial alterations that are pro-proliferative, pro-survival, and inflammatory changes similar to those caused by unopposed oestrogen.

• #26 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  A systematic review and meta-analysis by Renehan et al. (2008) demonstrated that, in premenopausal women, the risk of developing EC increases 1.59-fold with each 5 kg/m² increase in BMI at a BMI of 28 and above. […] There is a rising rate of obesity in developed nations, which is a likely cause of the increase in the incidence of endometrial carcinoma in the premenopausal population. […] Chronic hyperinsulinemia is tumorigenic in estrogen-sensitive tissues. […] The insulin-driven reduction of sex-hormone-binding globulin (SHBG) increases estrogen availability. […] Increased estradiol will stimulate endometrial cell proliferation and inhibit apoptosis, and it has been shown to stimulate insulin-like growth factor-I (IGF-I) in endometrial tissue. […] Polycystic Ovarian Syndrome (PCOS) is relatively common, affecting up to 8% of women, and polycystic ovaries (PCO) without the clinical diagnosis of PCOS affect up to 20% of women.

• #27 Endometrial cancer: Pathophysiology, diagnosis and management – IJCAAP

  https://www.ijcap.in/html-article/18885

  Tamoxifen therapy has been linked to an increased likelihood of developing EC even while it considerably lowers the risk of breast cancer and breast cancer recurrence. Tamoxifen is a selective oestrogen receptor modulator (SERM), which acts as an oestrogen antagonist in breast tissues but as an agonist in bone and endometrial tissues. Based on the majority of research, tamoxifen-using women had a 2-3 fold greater risk of developing EC than the general population. […] The majority of postmenopausal women who are diagnosed with EC are 60 years of age or older. Almost 85% of cases developing after the age of 50 and only 5% before the age of 40, the highest age-specific incidence occurs between the ages of 75 and 79. […] The metabolic syndrome raises the risk of diabetes, heart disease, stroke, and other chronic disease conditions. Hypertension, increased triglycerides, reduced HDL cholesterol, obesity, and hyperglycemia are major contributing factors to all possible causes of the metabolic syndrome. Epidemiologically, type 2 diabetes and hypertension have been linked to an increased risk of EC; however, the associated obesity is the hidden cause. […] The majority of ECs are triggered by sporadic mutations; however, only around 5% of EC instances are due to genetic alterations. Lynch syndrome and Cowden syndrome are examples of genetic predispositions that result in EC.

• #28 Tamoxifen and Uterine Cancer | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/06/tamoxifen-and-uterine-cancer

  Tamoxifen use may be extended to 10 years based on new data demonstrating additional benefit. […] Women taking tamoxifen should be informed about the risks of endometrial proliferation, endometrial hyperplasia, endometrial cancer, and uterine sarcomas. […] Postmenopausal women taking tamoxifen should be closely monitored for symptoms of endometrial hyperplasia or cancer. […] Unless the patient has been identified to be at high risk of endometrial cancer, routine endometrial surveillance has not proved to be effective in increasing the early detection of endometrial cancer in women using tamoxifen. […] Most studies have found that the increased relative risk of developing endometrial cancer for women taking tamoxifen is two to three times higher than that of an age-matched population.

• #29 Endometrial Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9421940/

  Endometrial cancer (EC) is often a hormone-sensitive disease thought to commonly arise in the context of excessive estrogenic stimulation of the endometrial lining of the uterus. This estrogenic stimulation leads to mitogenic stimulation, and ultimately, malignant transformation of the endometrial glandular epithelium, and accounts for the development of the more common and lower grade endometrioid ECs. Risk factors for hyperestrogenism include obesity, hormone therapy (such as tamoxifen), ovarian cortical hyperplasia (hyperthecosis), polycystic ovarian syndrome, and hormone-producing tumors. […] Endometrioid ECs develop through malignant transformation of the precursor lesions atypical endometrial hyperplasia (AEH) also known as endometrial intraepithelial neoplasia. AEH often contains somatic PTEN mutations; loss of PTEN is necessary for the development of AEH but is insufficient for progression to invasive carcinoma. ARID1A has a critical role in the transition of precursor AEH lesions to invasive endometrioid carcinomas, and inactivation of TGFB also contributes to the progression of AEH to invasive carcinoma.

• #30 Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis

  https://www.mdpi.com/2227-9059/12/4/886

  The condition is characterized by oligo- or anovulation, signs of androgen excess, and an excess of small ovarian cysts. […] Chronic anovulation leads to chronic estrogen exposure which, as stated above, can lead to endometrial hyperplasia and neoplasia. […] The association between PCOS and EC was described as early as 1949 and is based on several factors. […] Early treatment of PCOS may reduce the risk of the development of endometrial cancer by targeting BMI and insulin resistance. […] There is evidence that the incidence of EC in the premenopausal population continues to rise. […] The most commonly reported risk factors are obesity, nulliparity, longer duration of menses (earlier age at menarche or late age of menopause), a history of anovulatory cycles, PCOS, diabetes mellitus, and/or unopposed estrogen therapy.

• #31 Uterine (Endometrial) Cancer Risk Factors & Prevention | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/uterine-endometrial/risk-factors

  Before menopause, a womans ovaries normally produce two main types of hormones: estrogen and progesterone. Estrogen encourages the growth of endometrial cells in the uterus, whereas progesterone inhibits it. When a woman has high circulating levels of estrogen and low levels of progesterone over long periods of time, the risk for uterine (endometrial) cancer rises. […] The cells in fatty tissue also make estrogen, which helps explain why obesity (50 pounds or more overweight) is the biggest risk factor for developing this cancer. […] Women who inherit mutations in the PTEN gene (Cowdens syndrome) may also be at an increased risk of developing endometrial cancer.

• #32 Pathogenesis of Histological Types of Endometrial Cancer | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-540-37861-7_5

  Professor Horn discussed the pathogenesis of different histological types of endometrial carcinoma. […] The cause of type 2 carcinoma is unknown. […] Hyperestrogenism leads to hyperplasia and therefore may lead to atypical forms which may cause endometrioid adenocarcinoma. […] It appears that postmenopausal women with unopposed HRT have two to three times the risk of endometrial adenocarcinoma, and that cancer risk is reduced with the use of sequential HRT. […] The familial (endometrioid) endometrium carcinomas show fivefold increased risk. […] Apparently polyps are induced, which in rare cases develop into serous-papillary or clear-cell carcinomas. This affects primarily older women.

• #33 Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy

  https://www.mdpi.com/2072-6694/16/11/2027

  Genetic mutations are essential factors in the development and progression of EC. These mutations can affect a series of genes involved in different cellular processes, such as the regulation of cellular cycle, DNA repair, apoptosis, and hormonal signaling. […] The evolution of genetic and molecular studies has offered valuable information that has led to the current classification that describes four molecular subtypes of EC. […] Inactivation of the PTEN tumor suppressor gene is associated with the inactivation of other tumor suppressor genes, such as TP53 (p53) and ARID1A, in EC. […] Loss of function of these genes removes important regulatory mechanisms that normally inhibit tumor growth and promote apoptosis. […] Oncogenes, such as KRAS, CTNNB1 (β-catenin), and HER2/neu (human epidermal growth factor receptor 2), when mutated or activated, induce the stimulation of proliferation and extended survival of tumor cells, promoting the invasion and metastases of EC.

• #34 Endometrial cancer pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Endometrial_cancer_pathophysiology

  The TP53 pathway can either be suppressed or highly activated in endometrial cancer. When a mutant version of TP53 is overexpressed, the cancer tends to be particularly aggressive. TP53 mutations and chromosome instability are associated with serous carcinomas, which tend to resemble ovarian and fallopian carcinomas. Serous carcinomas are thought to develop from endometrial intraepithelial carcinoma. […] Mutations in tumor suppressor genes are common in type II endometrial cancer. PIK3CA is commonly mutated in both type I and type II cancers. In women with Lynch syndrome-associated endometrial cancer, microsatellite instability is common. […] The genetic mutations most commonly associated with endometrioid adenocarcinoma are in the genes PTEN, a tumor suppressor gene, PIK3CA (expresses a kinase), KRAS (expresses GTPase that functions in signal transduction), and CTNNB1 that expresses a protein involved in adhesion and cell signaling. The CTNNB1 (beta-catenin) gene is most commonly mutated in the squamous subtype of endometrioid adenocarcinoma. […] The genetic mutations seen in serous carcinoma are chromosomal instability and mutations in TP53, an important tumor suppressor gene.

• #35 Endometrial cancer: a genetic point of view – Bianco – Translational Cancer Research

  https://tcr.amegroups.org/article/view/46888/html

  Endometrial cancer has a heterogeneous pathophysiology, encompassing many histological types, microscopical features, pathogenesis, behaviors, and prognosis. […] Endometrial carcinomas have distinguishing molecular features. The most frequently mutated genes in endometrioid carcinomas are PTEN (77%), PIK3CA (53%), PIK3R1 (37%), CTNNB1 (36%), ARID1A (35%), K-RAS (24%), CTCF (20%), RPL22 (12%), TP53 (11%), FGFR2 (11%), and ARID5B (11%). […] Endometrial cancer presents more mutations than any other tumor type studied thus far in the PI3K/AKT pathway by TCGA. The PI3K-PTEN-AKT-mTOR signal transduction pathway regulates cell growth and survival, synthesis of specific proteins, and metabolism. […] The consequence of epigenetic silencing caused by promoter hypermethylation of MLH1 leads to MSI in sporadic endometrioid carcinomas. This results in the accumulation of somatic mutations at nucleotide repeats throughout the genome by defective MMR.

• #36 Molecular Pathogenesis of Endometrial Carcinoma | Oncohema Key

  https://oncohemakey.com/molecular-pathogenesis-of-endometrial-carcinoma/

  Molecular Pathogenesis of Endometrial Carcinoma The collective of endometrial carcinomas is increasingly recognized to comprise a number of distinct diseases. The major histologic types of endometrial carcinomas are associated with distinct molecular alterations. […] Three decades ago, the first characteristic molecular features for specific types of endometrial carcinomas were reported, with landmark papers describing TP53 mutation in nonendometrioid (serous) carcinomas, the identification of microsatellite instability in a significant portion of sporadic endometrial carcinomas, and PTEN mutation and CTNNB1 mutation in endometrioid types. […] The molecular characterization of endometrial carcinomas has been evolving, and an overview on the mutational landscape across histologic types as known today is given in Table 7-1. There are four major clinicopathologic variants of endometrial carcinomas that account for more than 95% of cases that differ with respect to molecular alterations, phenotype, biomarker expression, and clinical behavior.

• #37 Endometrial cancer pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Endometrial_cancer_pathophysiology

  The cancer usually first spreads into the myometrium and the serosa, then into other reproductive and pelvic structures. When the lymphatic system is involved, the pelvic lymph nodes and para-aortic lymph nodes are usually first to become involved, but in no specific pattern, unlike cervical cancer. […] More distant metastases are spread by the blood and often occur in the lungs, as well as the liver, brain, and bone. […] In 1020% of endometrial cancers, mostly grade 3 (the highest histologic grade), mutations are found in a tumor suppressor gene, commonly TP53 or PTEN. […] In 20% of endometrial hyperplasias and 50% of endometrioid cancers, PTEN suffers a loss-of-function mutation or a null mutation, making it less effective or completely ineffective. Loss of PTEN function leads to up-regulation of the PI3k/Akt/mTOR pathway, which causes cell growth.

• #38 Molecular Pathogenesis of Endometrial Carcinoma | Oncohema Key

  https://oncohemakey.com/molecular-pathogenesis-of-endometrial-carcinoma/

  PTEN/PI3K Pathway Mutations in the tumor suppressor gene PTEN occur in the majority of endometrioid carcinomas with a frequency of 83% in a selected series of endometrioid carcinomas that were associated with a precursor lesion such as endometrial intraepithelial neoplasia. PTEN is a dual specific phosphatase that is able to dephosphorylate both proteins and phospholipids. […] Loss of PTEN function accelerates signaling through the PI3K/AKT pathway. […] Activation of this pathway results in prevention of apoptosis, in addition to many other cellular effects. […] PTEN mutations result in loss of function due to frameshift mutations such as insertions or deletions (so called indels), which alter the reading frame. […] Some PTEN mutations are missense mutations that result from a point mutation that leads to substitution of an amino acid.

• #39 Endometrial cancer pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Endometrial_cancer_pathophysiology

  The TP53 pathway can either be suppressed or highly activated in endometrial cancer. When a mutant version of TP53 is overexpressed, the cancer tends to be particularly aggressive. TP53 mutations and chromosome instability are associated with serous carcinomas, which tend to resemble ovarian and fallopian carcinomas. Serous carcinomas are thought to develop from endometrial intraepithelial carcinoma. […] Mutations in tumor suppressor genes are common in type II endometrial cancer. PIK3CA is commonly mutated in both type I and type II cancers. In women with Lynch syndrome-associated endometrial cancer, microsatellite instability is common. […] The genetic mutations most commonly associated with endometrioid adenocarcinoma are in the genes PTEN, a tumor suppressor gene, PIK3CA (expresses a kinase), KRAS (expresses GTPase that functions in signal transduction), and CTNNB1 that expresses a protein involved in adhesion and cell signaling. The CTNNB1 (beta-catenin) gene is most commonly mutated in the squamous subtype of endometrioid adenocarcinoma. […] The genetic mutations seen in serous carcinoma are chromosomal instability and mutations in TP53, an important tumor suppressor gene.

• #40 Molecular Pathogenesis of Endometrial Carcinoma | Oncohema Key

  https://oncohemakey.com/molecular-pathogenesis-of-endometrial-carcinoma/

  Loss of PTEN expression is seen in approximately half of endometrioid carcinomas. […] PTEN mutations have been detected in endometrial hyperplasias, and focal loss of PTEN expression has been observed in approximately half of endometrial hyperplasia, either atypical or nonatypical. […] These data suggest that PTEN alterations are common, occur early, and provide a susceptibility background. Loss of PTEN function might be necessary but not sufficient for initiation of endometrioid carcinogenesis. […] PI3K is another pathway member that is frequently altered by activating mutations. […] Activating mutations in exon 3 of CTNNB1 have been reported in 45% of endometrioid carcinomas. […] Mutated CTNNB1 escapes this degradation, resulting in increased cytoplasmic level of CTNNB1, nuclear translocation, and enhanced participation in transcriptional regulation through the formation of bipartite complex with the TCF transcription factor. […] The Wnt signaling pathway is involved in pleiotropic cellular functions including differentiation. […] With respect to carcinogenesis, the antiapoptotic effects of the CTNNB1 mutation may be the major outcome of aberrant Wnt signaling.

• #41 Uterine Cancer: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/258148-overview

  Fibroblast growth factor receptor 2 (FGFR2) is a tyrosine kinase receptor involved in many biological processes. Mutations in FGFR2 have been reported in up to 10-12% of endometrial carcinomas. Inhibition of FGFR2 could be a therapeutic target in endometrial carcinoma. Gatius et al suggest that FGFR2 has a dual role in the endometrium, inhibiting cell proliferation in normal endometria during the menstrual cycle but acting as an oncogene in endometrial carcinoma. […] Endometrial cancers are divided into 2 classes, each with differing pathophysiology and prognosis. […] More than 80% of endometrial carcinomas are type I and are due to unopposed estrogen stimulation, resulting in a low-grade histology. It is often found in association with atypical endometrial hyperplasia, which is thought to be a precursor lesion. Type II endometrial cancers are thought to be estrogen independent, occurring in older women, with high-grade histologies such as uterine papillary serous or clear cell.

• #42 Endometrial cancer: a genetic point of view – Bianco – Translational Cancer Research

  https://tcr.amegroups.org/article/view/46888/html

  All types of serous carcinomas, except for a single tumor, belong to the high copy number subgroup in the TCGA classification. Mutations and/or dysregulation of TP53 or p53 are the most frequent molecular aberrations. […] Endometrial cancer risk may be influenced by common low-penetrance variants, such as single nucleotide variants (SNVs), in genes involved in cell survival, estrogen metabolism, and transcriptional control. […] The identification of biomarkers and their relationship with the risk factors are necessary for the improvement in risk stratification and early detection of endometrial cancers in view of the rise in disease incidence and mortality. […] Despite the involvement of genetic factors in the risk of endometrial cancer, they are not incorporated in the standard clinical procedures for prognosis assessment.

• #43 Endometrial cancer pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Endometrial_cancer_pathophysiology

  The TP53 pathway can either be suppressed or highly activated in endometrial cancer. When a mutant version of TP53 is overexpressed, the cancer tends to be particularly aggressive. TP53 mutations and chromosome instability are associated with serous carcinomas, which tend to resemble ovarian and fallopian carcinomas. Serous carcinomas are thought to develop from endometrial intraepithelial carcinoma. […] Mutations in tumor suppressor genes are common in type II endometrial cancer. PIK3CA is commonly mutated in both type I and type II cancers. In women with Lynch syndrome-associated endometrial cancer, microsatellite instability is common. […] The genetic mutations most commonly associated with endometrioid adenocarcinoma are in the genes PTEN, a tumor suppressor gene, PIK3CA (expresses a kinase), KRAS (expresses GTPase that functions in signal transduction), and CTNNB1 that expresses a protein involved in adhesion and cell signaling. The CTNNB1 (beta-catenin) gene is most commonly mutated in the squamous subtype of endometrioid adenocarcinoma. […] The genetic mutations seen in serous carcinoma are chromosomal instability and mutations in TP53, an important tumor suppressor gene.

• #44 Endometrial Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9421940/

  In this study, one subgroup was defined by widespread genomic alterations and extensive amplifications and deletions and was termed the copy number high (CNH) group. The CNH group contained most high-grade, aggressive cancers, and included all uterine serous carcinomas and ~25% of the high-grade endometrioid tumors. The clinical outcome of this subgroup was poor. Most of these tumors had pathogenetic mutations in TP53. These tumors also have frequent somatic mutations in PIK3CA, and mutations in FBXW7 and PPP2R1A, which are unique to CNH tumors. […] Another subgroup of EC was tumors with microsatellite instability (MSI). These tumors have mismatch repair defects and a tumor mutational burden that is ~10-fold greater than that of a general mutational background. These tumors have mutations in many genes owing to their generally high mutation burden, therefore, it can be difficult to differentiate passenger from driver mutations. PTEN, ARID1A, PIK3CA, PIK3R1 and RPL22 are all commonly mutated in the MSI subgroup of EC. Moreover, mutations or epigenetic silencing of MLH1, MSH2, MSH6, PMS2, and less commonly EPCAM, are often responsible for MSI.

• #45 Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy

  https://www.mdpi.com/2072-6694/16/11/2027

  Defects in DNA mismatch repair genes, such as MLH1, MSH2, MSH6, and PMS2, are associated with microsatellite instability-high (MSI-H) endometrial cancers. […] Hormonal signaling is an essential mechanism involved in the development and progression of EC. […] A dysregulation in hormonal signaling can induce abnormal proliferation, genomic instability, and angiogenesis inside the endometrium, thus predisposing to the development of EC. […] Epigenetic modifications occur in EC, involving DNA methylation, histone modification, and micro-RNA (miRNA) dysregulation, leading to aberrant gene expressions. […] Angiogenesis is a physiological process that ensures the formation of new blood vessels, and it contributes to wound healing and embryological development. In EC, the dysregulation of angiogenic signaling pathways leads to the abnormal formations of new blood vessels and so it contributes to tumor growth, invasion, and metastasis by providing oxygen and nutrients for tumor cells.

• #46 Endometrial Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9421940/

  In this study, one subgroup was defined by widespread genomic alterations and extensive amplifications and deletions and was termed the copy number high (CNH) group. The CNH group contained most high-grade, aggressive cancers, and included all uterine serous carcinomas and ~25% of the high-grade endometrioid tumors. The clinical outcome of this subgroup was poor. Most of these tumors had pathogenetic mutations in TP53. These tumors also have frequent somatic mutations in PIK3CA, and mutations in FBXW7 and PPP2R1A, which are unique to CNH tumors. […] Another subgroup of EC was tumors with microsatellite instability (MSI). These tumors have mismatch repair defects and a tumor mutational burden that is ~10-fold greater than that of a general mutational background. These tumors have mutations in many genes owing to their generally high mutation burden, therefore, it can be difficult to differentiate passenger from driver mutations. PTEN, ARID1A, PIK3CA, PIK3R1 and RPL22 are all commonly mutated in the MSI subgroup of EC. Moreover, mutations or epigenetic silencing of MLH1, MSH2, MSH6, PMS2, and less commonly EPCAM, are often responsible for MSI.

• #47 Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-6-22

  In endometrial cancers, MSI is very common and while a hallmark of LS, MSI is not equivalent to LS. […] Based on the above characteristics, in endometrial cancers, MSI detection is not specific thus not very helpful in the diagnosis of LS. […] It is being recognized that, in LS, the risk of EC is equal to, or higher than the risk of CRC. […] Lifetime risk of LS-related EC is associated with age and a mutation of a specific MMR gene. […] Patients with MSH6 mutations are at higher risk (64-71%) for developing EC than those with MSH2 or MLH1 mutations (40-50%). […] It has long been thought that LS-related EC occurs at younger ages than in sporadic cases. […] In fact, others have described that 25% of LS patients do not fit standard screening criteria, such as the Amsterdam, Bethesda, and SGO criteria, where age is a prominent factor (cut-off age 50).

• #48 Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-6-22

  Lynch syndrome (LS), an autosomal dominant inherited cancer susceptibility syndrome, also known as hereditary non-polyposis colon cancer (HNPCC), is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. […] More recently, it is found that a similar number of endometrial cancers is also due to one of the MMR gene mutations. […] There has been significant progress in LS-related CRC in terms of molecular pathogenesis, risks, genetic basis, and cancer prevention. In contrast, the advance about LS-related endometrial cancer (EC) is very much limited. […] Recently, focus has shifted to LS-related endometrial cancer (EC) as women with LS have a 40-60% chance of presenting with EC as the first clinical manifestation. […] The main function of MMR is to maintain genomic stability by correcting mismatches generated during DNA replication. MMR malfunction results in a mutated phenotype and microsatellite instability (MSI), which promotes cancer formation.

• #49 Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-6-22

  In endometrial cancers, MSI is very common and while a hallmark of LS, MSI is not equivalent to LS. […] Based on the above characteristics, in endometrial cancers, MSI detection is not specific thus not very helpful in the diagnosis of LS. […] It is being recognized that, in LS, the risk of EC is equal to, or higher than the risk of CRC. […] Lifetime risk of LS-related EC is associated with age and a mutation of a specific MMR gene. […] Patients with MSH6 mutations are at higher risk (64-71%) for developing EC than those with MSH2 or MLH1 mutations (40-50%). […] It has long been thought that LS-related EC occurs at younger ages than in sporadic cases. […] In fact, others have described that 25% of LS patients do not fit standard screening criteria, such as the Amsterdam, Bethesda, and SGO criteria, where age is a prominent factor (cut-off age 50).

• #50 Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-6-22

  In endometrial cancers, MSI is very common and while a hallmark of LS, MSI is not equivalent to LS. […] Based on the above characteristics, in endometrial cancers, MSI detection is not specific thus not very helpful in the diagnosis of LS. […] It is being recognized that, in LS, the risk of EC is equal to, or higher than the risk of CRC. […] Lifetime risk of LS-related EC is associated with age and a mutation of a specific MMR gene. […] Patients with MSH6 mutations are at higher risk (64-71%) for developing EC than those with MSH2 or MLH1 mutations (40-50%). […] It has long been thought that LS-related EC occurs at younger ages than in sporadic cases. […] In fact, others have described that 25% of LS patients do not fit standard screening criteria, such as the Amsterdam, Bethesda, and SGO criteria, where age is a prominent factor (cut-off age 50).

• #51 Endometrial Cancer Overview – Signaling Pathway. Diagnostics Marker. Targeted Therapy and Clinical Trials.

  https://www.antibody-creativebiolabs.com/endometrial-cancer-overview-signaling-pathway.htm

  Endometrial cancer (EC) is the most common gynecologic malignancy. […] The endometrial cancer is the most common gynecologic malignancy that starts in the endometrium of women. Carcinogenesis of EC is associated with several critical regulatory molecules, which involve in different signaling pathways. A number of signaling pathways have been identified to be involved in the multiple-step development of EC, including PI3K/AKT/mTOR signaling pathway, WNT/-catenin signal transduction cascades (including APC/-catenin pathway), MAPK/ERK pathway, VEGF/VEGFR ligand receptor signaling pathway, ErbB signaling pathway, P53/P21 and P16INK4a/pRB signaling pathways. Based on the fundamental biological function of these signaling pathways and pathological features of EC, four capabilities of transforming endometrial cells are critical to the primary carcinogenesis and metastasis: 1) evading apoptosis, 2) enhancing cell proliferation, 3) blocking differentiation, 4) inducing angiogenesis. At the same time, above molecular mechanisms also provide multiple potential targets for the treatment of endometrial cancer.

• #52 Endometrial Cancer Overview – Signaling Pathway. Diagnostics Marker. Targeted Therapy and Clinical Trials.

  https://www.antibody-creativebiolabs.com/endometrial-cancer-overview-signaling-pathway.htm

  RTK signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of basic biological processes of cells such as metabolism, growth, proliferation, survival and angiogenesis. mTOR pathway was identified to be activated during tumor formation and PTEN gene mutations, which plays a role in cellular signaling by inhibiting the MAPK kinase pathway, were associated with the histology, early stage, and favorable clinical behavior of endometrial cancers. MAPK regulates cell proliferation and differentiation via RAF-MEK-ERK signaling cascade. The ErbB receptors are mediators of cell proliferation, migration, differentiation, apoptosis, and cell motility by signaling transduction. Activation of AKT is closely associated with endometrial carcinogenesis and prognosis by controlling specific gene expression, thereafter occurs new hallmarks for cell transformation such as angiogenesis, evading apoptosis, enhancing proliferation and blocking differentiation. VEGFs and the angiopoietins are key factors in angiogenesis and play a significant role to myometrial invasion and lymph node metastasis.

• #53 Mechanism of Tetrandrine Against Endometrial Cancer – DDDT | DDDT

  https://www.dovepress.com/mechanism-of-tetrandrine-against-endometrial-cancer-based-on-network-p-peer-reviewed-fulltext-article-DDDT

  The PI3K/Akt pathway is one of the most frequently dysregulated pathways in cancer that regulates cell proliferation, growth, cell size, metabolism, and motility. […] Therefore, to verify the prediction that we obtained from biological data mining, we determined the expressions of Akt and p-Akt by using Western blot assays. […] Taken together, these results revealed that tetrandrine exerted tumour suppressive effects on EC by regulating the PI3K/Akt signalling pathway.

• #54 Endometrial Cancer Overview – Signaling Pathway. Diagnostics Marker. Targeted Therapy and Clinical Trials.

  https://www.antibody-creativebiolabs.com/endometrial-cancer-overview-signaling-pathway.htm

  The Wnt signaling pathway is one of the most evolutionary-conserved signal transduction pathways. The Wnt signaling pathways include -catenin dependent Wnt signaling pathway (i.e. canonical Wnt/-catenin) and -catenin independent Wnt signaling pathway (i.e. Non-canonical, such as Wnt/JNK pathway, Wnt/calcium pathway). Among these Wnt signaling pathways, the -catenin dependent pathway has been associated with human endometrial cancer. For canonical Wnt signaling pathways, the major effector is the transcription factor -catenin. Moreover, progesterone could inhibit Wnt signaling by induction of DKK1 and FOXO1 expression, the inhibition of Wnt signaling by progesterone was partly circumvented in Wnt activated Ishikawa cells. During the menstrual cycle, estradiol can enhance Wnt/-catenin signaling, and constitutive activation of Wnt/-catenin signaling will cause endometrial hyperplasia, which may develop further into endometrial cancer.

• #55 Endometrial Cancer Overview – Signaling Pathway. Diagnostics Marker. Targeted Therapy and Clinical Trials.

  https://www.antibody-creativebiolabs.com/endometrial-cancer-overview-signaling-pathway.htm

  RTK signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of basic biological processes of cells such as metabolism, growth, proliferation, survival and angiogenesis. mTOR pathway was identified to be activated during tumor formation and PTEN gene mutations, which plays a role in cellular signaling by inhibiting the MAPK kinase pathway, were associated with the histology, early stage, and favorable clinical behavior of endometrial cancers. MAPK regulates cell proliferation and differentiation via RAF-MEK-ERK signaling cascade. The ErbB receptors are mediators of cell proliferation, migration, differentiation, apoptosis, and cell motility by signaling transduction. Activation of AKT is closely associated with endometrial carcinogenesis and prognosis by controlling specific gene expression, thereafter occurs new hallmarks for cell transformation such as angiogenesis, evading apoptosis, enhancing proliferation and blocking differentiation. VEGFs and the angiopoietins are key factors in angiogenesis and play a significant role to myometrial invasion and lymph node metastasis.

• #56 Endometrial Cancer Overview – Signaling Pathway. Diagnostics Marker. Targeted Therapy and Clinical Trials.

  https://www.antibody-creativebiolabs.com/endometrial-cancer-overview-signaling-pathway.htm

  RTK signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of basic biological processes of cells such as metabolism, growth, proliferation, survival and angiogenesis. mTOR pathway was identified to be activated during tumor formation and PTEN gene mutations, which plays a role in cellular signaling by inhibiting the MAPK kinase pathway, were associated with the histology, early stage, and favorable clinical behavior of endometrial cancers. MAPK regulates cell proliferation and differentiation via RAF-MEK-ERK signaling cascade. The ErbB receptors are mediators of cell proliferation, migration, differentiation, apoptosis, and cell motility by signaling transduction. Activation of AKT is closely associated with endometrial carcinogenesis and prognosis by controlling specific gene expression, thereafter occurs new hallmarks for cell transformation such as angiogenesis, evading apoptosis, enhancing proliferation and blocking differentiation. VEGFs and the angiopoietins are key factors in angiogenesis and play a significant role to myometrial invasion and lymph node metastasis.

• #57 Endometrial Cancer Overview – Signaling Pathway. Diagnostics Marker. Targeted Therapy and Clinical Trials.

  https://www.antibody-creativebiolabs.com/endometrial-cancer-overview-signaling-pathway.htm

  RTK signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of basic biological processes of cells such as metabolism, growth, proliferation, survival and angiogenesis. mTOR pathway was identified to be activated during tumor formation and PTEN gene mutations, which plays a role in cellular signaling by inhibiting the MAPK kinase pathway, were associated with the histology, early stage, and favorable clinical behavior of endometrial cancers. MAPK regulates cell proliferation and differentiation via RAF-MEK-ERK signaling cascade. The ErbB receptors are mediators of cell proliferation, migration, differentiation, apoptosis, and cell motility by signaling transduction. Activation of AKT is closely associated with endometrial carcinogenesis and prognosis by controlling specific gene expression, thereafter occurs new hallmarks for cell transformation such as angiogenesis, evading apoptosis, enhancing proliferation and blocking differentiation. VEGFs and the angiopoietins are key factors in angiogenesis and play a significant role to myometrial invasion and lymph node metastasis.

• #58 Endometrial Cancer Overview – Signaling Pathway. Diagnostics Marker. Targeted Therapy and Clinical Trials.

  https://www.antibody-creativebiolabs.com/endometrial-cancer-overview-signaling-pathway.htm

  Notch signaling pathway is a highly conservative pathways, which have an important role in cell proliferation, differentiation and apoptosis. Notch signaling pathway starts in the form of through the ligand binding, then Notch1 receptor proteolytic cracking in the film, in order to release the Notch intracellular structure domain (NICD) activity. Then transferred to the nucleus and as transcription activator, in order to improve the target genes, such as HES1 expression. In addition, pathway can lead to tumorigenesis, related to duration, cell type and background. The research show Notch signaling pathway is a key factor regulating cell proliferation activity in endometrial cancer. […] Apoptosis disorders are among the many mechanisms significant in carcinogenesis. One of the most extensively researched genes that takes part in apoptosis is the TP53 gene. Abnormal p53 protein production due to gene mutation leads to an inability to repair the damaged DNA and as a result, via complex mechanisms, to uncontrollable cancer cell growth and the presence of mutations in gene TP53, which is associated with statistically significant shorter patient survival, occurs in 17-61% of endometrioid cancers. The P16 gene is responsible for cell proliferation in the G1 phase. Its alterations and abnormal epigenetic modifications for are also play an important role during EC carcinogenesis.

• #59 Endometrial Cancer Overview – Signaling Pathway. Diagnostics Marker. Targeted Therapy and Clinical Trials.

  https://www.antibody-creativebiolabs.com/endometrial-cancer-overview-signaling-pathway.htm

  Notch signaling pathway is a highly conservative pathways, which have an important role in cell proliferation, differentiation and apoptosis. Notch signaling pathway starts in the form of through the ligand binding, then Notch1 receptor proteolytic cracking in the film, in order to release the Notch intracellular structure domain (NICD) activity. Then transferred to the nucleus and as transcription activator, in order to improve the target genes, such as HES1 expression. In addition, pathway can lead to tumorigenesis, related to duration, cell type and background. The research show Notch signaling pathway is a key factor regulating cell proliferation activity in endometrial cancer. […] Apoptosis disorders are among the many mechanisms significant in carcinogenesis. One of the most extensively researched genes that takes part in apoptosis is the TP53 gene. Abnormal p53 protein production due to gene mutation leads to an inability to repair the damaged DNA and as a result, via complex mechanisms, to uncontrollable cancer cell growth and the presence of mutations in gene TP53, which is associated with statistically significant shorter patient survival, occurs in 17-61% of endometrioid cancers. The P16 gene is responsible for cell proliferation in the G1 phase. Its alterations and abnormal epigenetic modifications for are also play an important role during EC carcinogenesis.

• #60 Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy

  https://www.mdpi.com/2072-6694/16/11/2027

  Defects in DNA mismatch repair genes, such as MLH1, MSH2, MSH6, and PMS2, are associated with microsatellite instability-high (MSI-H) endometrial cancers. […] Hormonal signaling is an essential mechanism involved in the development and progression of EC. […] A dysregulation in hormonal signaling can induce abnormal proliferation, genomic instability, and angiogenesis inside the endometrium, thus predisposing to the development of EC. […] Epigenetic modifications occur in EC, involving DNA methylation, histone modification, and micro-RNA (miRNA) dysregulation, leading to aberrant gene expressions. […] Angiogenesis is a physiological process that ensures the formation of new blood vessels, and it contributes to wound healing and embryological development. In EC, the dysregulation of angiogenic signaling pathways leads to the abnormal formations of new blood vessels and so it contributes to tumor growth, invasion, and metastasis by providing oxygen and nutrients for tumor cells.

• #61 DNA Methylation Machinery in the Endometrium and Endometrial Cancer | Anticancer Research

  https://ar.iiarjournals.org/content/36/9/4407

  Epigenetic changes including DNA methylation, covalent histone modifications, nucleosome positioning and non-coding RNA molecules are increasingly regarded as key events in the development of endometrial cancer. […] Deregulation of DNA methylation proteins can thus disrupt cell homeostasis of the endometrium. There is increased evidence that an aberrant DNA methylation pattern can result in various pathological forms of the endometrium and in endometrial cancer development. […] Similar to other types of cancer, endometrial cancer cells acquire two main types of aberrant DNA methylation pattern during malignant transformation: global DNA demethylation/hypomethylation and local DNA hypermethylation. […] An aberrant DNA methylation pattern can be one of the major mechanisms which promote the ability of cancer cells to evade apoptosis and thus contribute to therapeutic resistance. […] The inability of cancer cells to respond to apoptotic stimuli is a major problem in successful anticancer therapy.

• #62 DNA Methylation Machinery in the Endometrium and Endometrial Cancer | Anticancer Research

  https://ar.iiarjournals.org/content/36/9/4407

  Epigenetic changes including DNA methylation, covalent histone modifications, nucleosome positioning and non-coding RNA molecules are increasingly regarded as key events in the development of endometrial cancer. […] Deregulation of DNA methylation proteins can thus disrupt cell homeostasis of the endometrium. There is increased evidence that an aberrant DNA methylation pattern can result in various pathological forms of the endometrium and in endometrial cancer development. […] Similar to other types of cancer, endometrial cancer cells acquire two main types of aberrant DNA methylation pattern during malignant transformation: global DNA demethylation/hypomethylation and local DNA hypermethylation. […] An aberrant DNA methylation pattern can be one of the major mechanisms which promote the ability of cancer cells to evade apoptosis and thus contribute to therapeutic resistance. […] The inability of cancer cells to respond to apoptotic stimuli is a major problem in successful anticancer therapy.

• #63 Endometrial cancer: a genetic point of view – Bianco – Translational Cancer Research

  https://tcr.amegroups.org/article/view/46888/html

  Endometrial cancer has a heterogeneous pathophysiology, encompassing many histological types, microscopical features, pathogenesis, behaviors, and prognosis. […] Endometrial carcinomas have distinguishing molecular features. The most frequently mutated genes in endometrioid carcinomas are PTEN (77%), PIK3CA (53%), PIK3R1 (37%), CTNNB1 (36%), ARID1A (35%), K-RAS (24%), CTCF (20%), RPL22 (12%), TP53 (11%), FGFR2 (11%), and ARID5B (11%). […] Endometrial cancer presents more mutations than any other tumor type studied thus far in the PI3K/AKT pathway by TCGA. The PI3K-PTEN-AKT-mTOR signal transduction pathway regulates cell growth and survival, synthesis of specific proteins, and metabolism. […] The consequence of epigenetic silencing caused by promoter hypermethylation of MLH1 leads to MSI in sporadic endometrioid carcinomas. This results in the accumulation of somatic mutations at nucleotide repeats throughout the genome by defective MMR.

• #64 Endometrial Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK525981/

  The molecular etiologies of high-grade endometrioid and clear cell endometrial carcinomas lack the definition achieved by research on the pathogenesis of endometrial low-grade endometrioid carcinomas and endometrial serous carcinomas. […] Immunologic mechanisms also contribute to malignant endometrial transformation. While the immune system is normally protective against pathogenic changes, study results have identified immunologic factors that promote progression from EIN to endometrial cancer, including tumor-associated macrophages, fibroblasts, and myofibroblasts.

• #65 dMMR and Endometrial Cancer | JEMPERLI (dostarlimab-gxly)

  https://www.jemperlihcp.com/endometrial-cancer/

  Cancer cells can increase expression of PD-L1 on their surface, which binds to PD-1 on T cells. […] This reduces the immune system’s ability to identify and attack the cancer cells. […] JEMPERLI binds to PD-1 receptors on the T cells, blocking PD-L1 or PD-L2 interactions. […] This enables T cells to identify and attack cancer cells by restoring cytotoxic activity in the T cell. […] JEMPERLI harnesses the power of the immune system.

• #66 Biomolecular basis related to inflammation in the pathogenesis of endometrial cancer

  https://www.europeanreview.org/article/16038

  Endometrial cancer (EC) is a complex gynecological neoplasm with several clinical, histopathological and genetic features. Different hormonal, metabolic and biochemical axes are involved in pathogenesis. […] Indeed, inflammation is related to the pathogenesis of different tumors, including EC. […] Tumor Necrosis Factor-, Interleukin-6, Interleukin-1 Receptor Antagonist, Nuclear Factor-kB, Leptin, Adiponectin and C Reactive Protein were studied for cancer risk prediction models, risk stratification or targeted therapies. Furthermore, genetic studies evaluated the effect of inflammatory cytokines secreted by visceral adipocytes in the modulation of angiogenesis and signaling pathways such as PI3K/AKT/mTOR, that result altered in the pathogenesis of EC. […] The identification of inflammatory biomarkers released by adipose tissue, in the pathogenesis of EC, could be useful in improving diagnostic accuracy, identifying targets of therapy, suggesting useful lifestyle behaviors. A deeper knowledge of the genetic background of alterations in inflammatory pathway genes could better define the population exposed to a higher susceptibility to EC due to genetic polymorphisms. Future studies are needed to better understand this field.

• #67 Uterine Cancer: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/258148-overview

  Endometrial cancer may originate in a small area (eg, within an endometrial polyp) or in a diffuse multifocal pattern. Early tumor growth is characterized by an exophytic and spreading pattern. This growth is characterized by friability and spontaneous bleeding, even at early stages. Later tumor growth is characterized by myometrial invasion and growth toward the cervix. […] Four routes of spread occur beyond the uterus: Direct/local spread accounts for most local extension beyond the uterus. Lymphatic spread accounts for spread to pelvic, para-aortic, and, rarely, inguinal lymph nodes. Hematologic spread is responsible for metastases to the lungs, liver, bone, and brain (rare). Peritoneal/transtubal spread results in intraperitoneal implants, particularly with uterine papillary serous carcinoma (UPSC), similar to the pattern observed in ovarian cancer.

• #68 Uterine Cancer: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/258148-overview

  Endometrial cancer may originate in a small area (eg, within an endometrial polyp) or in a diffuse multifocal pattern. Early tumor growth is characterized by an exophytic and spreading pattern. This growth is characterized by friability and spontaneous bleeding, even at early stages. Later tumor growth is characterized by myometrial invasion and growth toward the cervix. […] Four routes of spread occur beyond the uterus: Direct/local spread accounts for most local extension beyond the uterus. Lymphatic spread accounts for spread to pelvic, para-aortic, and, rarely, inguinal lymph nodes. Hematologic spread is responsible for metastases to the lungs, liver, bone, and brain (rare). Peritoneal/transtubal spread results in intraperitoneal implants, particularly with uterine papillary serous carcinoma (UPSC), similar to the pattern observed in ovarian cancer.

• #69 Endometrial cancer pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Endometrial_cancer_pathophysiology

  The cancer usually first spreads into the myometrium and the serosa, then into other reproductive and pelvic structures. When the lymphatic system is involved, the pelvic lymph nodes and para-aortic lymph nodes are usually first to become involved, but in no specific pattern, unlike cervical cancer. […] More distant metastases are spread by the blood and often occur in the lungs, as well as the liver, brain, and bone. […] In 1020% of endometrial cancers, mostly grade 3 (the highest histologic grade), mutations are found in a tumor suppressor gene, commonly TP53 or PTEN. […] In 20% of endometrial hyperplasias and 50% of endometrioid cancers, PTEN suffers a loss-of-function mutation or a null mutation, making it less effective or completely ineffective. Loss of PTEN function leads to up-regulation of the PI3k/Akt/mTOR pathway, which causes cell growth.

• #70 Pathology of Endometrial Carcinoma | GLOWM

  https://www.glowm.com/section-view/heading/Pathology%20of%20Endometrial%20Carcinoma/item/238

  Depth of myometrial invasion has proven to be an independent predictor of outcome in early-stage endometrial carcinoma. Increasing depth of myometrial invasion is associated with a greater probability of nodal metastasis and death from tumor, even when adjusted for histologic grade and subtype. Vascular invasion is an important predictor of recurrence; its presence should always be stated in the pathology report. The incidence of vascular space invasion is higher in serous and clear cell types, but it may be present in any cell type. When observed, the risk of metastasis to pelvic and para-aortic lymph nodes increases significantly. […] Provocative studies investigating hormone receptor status and genetic alterations in endometrial carcinoma have been reported recently. Expression of estrogen receptors and progesterone receptors is found in most endometrial carcinomas, but in amounts lower than can be identified in normal cycling endometrium. Although neither ER nor PR expression correlates with stage, myometrial invasion, or lymph node metastasis, many recent reports suggest that expression of PR correlates with low tumor grade, low recurrence rate, and higher survival. Conversely, the absence of PR is associated with a worse prognosis. High-grade tumors such as serous and clear cell carcinoma tend to be negative, with antibodies directed toward ER and PR. Mutations of p53 have been identified in endometrial carcinoma and hyperplasia. Inactivation of this suppressor gene occurs at a much more frequent rate in high-grade and high-stage endometrial cancers such as serous carcinoma than in well-differentiated carcinomas and hyperplasia.

• #71 Pathology of Endometrial Carcinoma | GLOWM

  https://www.glowm.com/section-view/heading/Pathology%20of%20Endometrial%20Carcinoma/item/238

  Depth of myometrial invasion has proven to be an independent predictor of outcome in early-stage endometrial carcinoma. Increasing depth of myometrial invasion is associated with a greater probability of nodal metastasis and death from tumor, even when adjusted for histologic grade and subtype. Vascular invasion is an important predictor of recurrence; its presence should always be stated in the pathology report. The incidence of vascular space invasion is higher in serous and clear cell types, but it may be present in any cell type. When observed, the risk of metastasis to pelvic and para-aortic lymph nodes increases significantly. […] Provocative studies investigating hormone receptor status and genetic alterations in endometrial carcinoma have been reported recently. Expression of estrogen receptors and progesterone receptors is found in most endometrial carcinomas, but in amounts lower than can be identified in normal cycling endometrium. Although neither ER nor PR expression correlates with stage, myometrial invasion, or lymph node metastasis, many recent reports suggest that expression of PR correlates with low tumor grade, low recurrence rate, and higher survival. Conversely, the absence of PR is associated with a worse prognosis. High-grade tumors such as serous and clear cell carcinoma tend to be negative, with antibodies directed toward ER and PR. Mutations of p53 have been identified in endometrial carcinoma and hyperplasia. Inactivation of this suppressor gene occurs at a much more frequent rate in high-grade and high-stage endometrial cancers such as serous carcinoma than in well-differentiated carcinomas and hyperplasia.

• #72 Theories of Endometrial Carcinogenesis: A Multidisciplinary Approach | Modern Pathology

  https://www.nature.com/articles/3880051

  Based on these data regarding the pathogenesis of endometrioid and serous carcinoma, we have proposed a dualistic model of endometrial carcinogenesis incorporating a classic estrogen-driven pathway and an alternative pathway seemingly unrelated to hormones. […] The goal of this review is to propose a dualistic model of endometrial carcinogenesis that incorporates two pathways that differ in regard to epidemiologic risk factors, histopathologic lesions, and molecular events. […] The classic pathway is proposed as a mechanism by which indolent tumors develop from hyperplastic precursors in an estrogen-rich milieu. In contrast, the alternative pathway is thought to account for the development of many aggressive tumors that are not associated with hyperplasia or estrogen excess. […] According to this model, type 1 tumors are indolent neoplasms that are associated with hyperlipidemia, obesity, and signs of hyperestrogenism, such as anovulatory bleeding, infertility, late menopause, and endometrial and ovarian stromal hyperplasia. Type 2 tumors are unrelated to these features, behave aggressively, and lack the progesterone responsiveness of type 1 tumors.

• #73 Pathology of Endometrial Carcinoma | GLOWM

  https://www.glowm.com/section-view/heading/Pathology%20of%20Endometrial%20Carcinoma/item/238

  Endometrial carcinomas with associated hyperplasia tend to be well differentiated and have lesser degrees of myometrial invasion than lesions without such an association. Exogenous estrogen users have better-differentiated tumors than women who do not use estrogen. More aggressive variants of endometrial carcinoma, such as serous and clear cell carcinoma, are usually not associated with or preceded by hyperplasia. These data suggest that two classifications of endometrial carcinoma exist. One group, accounting for 65% of cases, is found in association with a high estrogen state, either endogenous or exogenous, and occurs in perimenopausal white women. This is usually a low-grade carcinoma of favorable prognosis, often accompanied by or preceded by hyperplasia, and has minimal myometrial invasion. The second type has no known predisposing conditions or any association with exogenous estrogen use or endometrial hyperplasia. These lesions are usually high-grade, aggressive neoplasms occurring in postmenopausal women, often disproportionately of Asian or African-American descent.

• #74 Endometrial Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK525981/

  Endometrial cancer is a malignancy originating within the epithelial lining of the uterus. […] The condition has historically been classified into type 1 and type 2 endometrial cancer based on histological characteristics. However, results from recent studies have begun classifying endometrial cancers according to a current molecular subgrouping system. Type 1 cancers are more common, with 80% of all endometrial cancers of endometrioid origin. Type 2 endometrial cancers are primarily of serous or clear cell origin. The most significant risk factors associated with endometrial cancer development include those that increase long-term exposure to unopposed estrogen (eg, obesity and exogenous estrogen). […] Present consensus holds that the pathogenesis of most low-grade endometrial carcinomas begins with uninterrupted endometrial proliferation, hormonally stimulated by endogenous or exogenous estrogen unopposed by progesterone or progestins, progressing through states of simple to complex forms of endometrial hyperplasia.

• #75 Theories of Endometrial Carcinogenesis: A Multidisciplinary Approach | Modern Pathology

  https://www.nature.com/articles/3880051

  Based on these data regarding the pathogenesis of endometrioid and serous carcinoma, we have proposed a dualistic model of endometrial carcinogenesis incorporating a classic estrogen-driven pathway and an alternative pathway seemingly unrelated to hormones. […] The goal of this review is to propose a dualistic model of endometrial carcinogenesis that incorporates two pathways that differ in regard to epidemiologic risk factors, histopathologic lesions, and molecular events. […] The classic pathway is proposed as a mechanism by which indolent tumors develop from hyperplastic precursors in an estrogen-rich milieu. In contrast, the alternative pathway is thought to account for the development of many aggressive tumors that are not associated with hyperplasia or estrogen excess. […] According to this model, type 1 tumors are indolent neoplasms that are associated with hyperlipidemia, obesity, and signs of hyperestrogenism, such as anovulatory bleeding, infertility, late menopause, and endometrial and ovarian stromal hyperplasia. Type 2 tumors are unrelated to these features, behave aggressively, and lack the progesterone responsiveness of type 1 tumors.

• #76 Endometrial Carcinoma: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/254083-overview

  The most widely used anticancer drug is tamoxifen, and this drug has been suggested by some studies to cause an increased incidence of adenocarcinoma of the endometrium. […] In contrast to tamoxifen, increasing data indicate that the use of combination oral contraceptives (OCs) decreases the risk of developing endometrial cancer. […] Some associated medical conditions have been found to increase the incidence of endometrial cancer. […] Data suggest that women who have had breast cancer have a 2- to 3-fold increased risk of subsequently developing endometrial cancer. […] Women who have hereditary nonpolyposis colon cancer (HNPCC) appear to have a markedly increased risk for developing endometrial cancer. […] The first type occurs in women who fall into the classic category. These women are obese and have hyperlipidemia, signs of hyperestrogenism, uterine bleeding, infertility, and late onset of menopause.

• #77

  https://link.springer.com/article/10.1007/BF02664933

  Molecular genetic evidence indicates that endometrial carcinoma likely develops as the result of a multistep process of oncogene activation and tumor suppressor gene inactivation. […] These molecular alterations appear to be specific for Type I (endometrioid) and Type II (non endometrioid) cancers. Type I cancers are characterized by mutation of PTEN, KRAS2, defects in DNA mismatch repair, as evidenced by the microsatellite instability phenotype, and a near diploid karyotype. Type II cancers often contain mutations of TP53 and Her-2/neu and are usually nondiploid. […] Furthermore, some of these tumor biomarkers constitute the targets for emerging therapies. […] Additional translational research is needed to identify molecular and genetic alterations with potential for therapeutic interventions.

• #78 Pathology of Endometrial Carcinoma | GLOWM

  https://www.glowm.com/section-view/heading/Pathology%20of%20Endometrial%20Carcinoma/item/238

  Endometrial carcinomas with associated hyperplasia tend to be well differentiated and have lesser degrees of myometrial invasion than lesions without such an association. Exogenous estrogen users have better-differentiated tumors than women who do not use estrogen. More aggressive variants of endometrial carcinoma, such as serous and clear cell carcinoma, are usually not associated with or preceded by hyperplasia. These data suggest that two classifications of endometrial carcinoma exist. One group, accounting for 65% of cases, is found in association with a high estrogen state, either endogenous or exogenous, and occurs in perimenopausal white women. This is usually a low-grade carcinoma of favorable prognosis, often accompanied by or preceded by hyperplasia, and has minimal myometrial invasion. The second type has no known predisposing conditions or any association with exogenous estrogen use or endometrial hyperplasia. These lesions are usually high-grade, aggressive neoplasms occurring in postmenopausal women, often disproportionately of Asian or African-American descent.

• #79 Pathology of Endometrial Carcinoma | GLOWM

  https://www.glowm.com/section-view/heading/Pathology%20of%20Endometrial%20Carcinoma/item/238

  Depth of myometrial invasion has proven to be an independent predictor of outcome in early-stage endometrial carcinoma. Increasing depth of myometrial invasion is associated with a greater probability of nodal metastasis and death from tumor, even when adjusted for histologic grade and subtype. Vascular invasion is an important predictor of recurrence; its presence should always be stated in the pathology report. The incidence of vascular space invasion is higher in serous and clear cell types, but it may be present in any cell type. When observed, the risk of metastasis to pelvic and para-aortic lymph nodes increases significantly. […] Provocative studies investigating hormone receptor status and genetic alterations in endometrial carcinoma have been reported recently. Expression of estrogen receptors and progesterone receptors is found in most endometrial carcinomas, but in amounts lower than can be identified in normal cycling endometrium. Although neither ER nor PR expression correlates with stage, myometrial invasion, or lymph node metastasis, many recent reports suggest that expression of PR correlates with low tumor grade, low recurrence rate, and higher survival. Conversely, the absence of PR is associated with a worse prognosis. High-grade tumors such as serous and clear cell carcinoma tend to be negative, with antibodies directed toward ER and PR. Mutations of p53 have been identified in endometrial carcinoma and hyperplasia. Inactivation of this suppressor gene occurs at a much more frequent rate in high-grade and high-stage endometrial cancers such as serous carcinoma than in well-differentiated carcinomas and hyperplasia.

• #80 Uterine Cancer: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/258148-overview

  Less histologic differentiation is associated with a higher incidence of deep myometrial invasion and lymph node metastases. Subsequently, the depth of myometrial invasion and presence of tumor in the lymph nodes is directly related to recurrence rates and 5-year survival rates. […] PTEN mutation is thought to be an early event in low-grade endometrial cancers and is found in 55% of hyperplasia and 85% of cancers, whereas it is not found in benign endometrium. […] Approximately 15-20% of endometrial cancers are type II cancers with papillary serous or clear cell histologies. Papillary serous histology represents 5-10% and clear cell histology represents less than 5% of endometrial cancers. They are considered high grade with poor prognosis. […] The p53 mutation is more common in high-grade tumors, and ERBB-2 (HER-2/neu) mutation is common in type II cancers.

• #81 Theories of Endometrial Carcinogenesis: A Multidisciplinary Approach | Modern Pathology

  https://www.nature.com/articles/3880051

  Based on these data regarding the pathogenesis of endometrioid and serous carcinoma, we have proposed a dualistic model of endometrial carcinogenesis incorporating a classic estrogen-driven pathway and an alternative pathway seemingly unrelated to hormones. […] The goal of this review is to propose a dualistic model of endometrial carcinogenesis that incorporates two pathways that differ in regard to epidemiologic risk factors, histopathologic lesions, and molecular events. […] The classic pathway is proposed as a mechanism by which indolent tumors develop from hyperplastic precursors in an estrogen-rich milieu. In contrast, the alternative pathway is thought to account for the development of many aggressive tumors that are not associated with hyperplasia or estrogen excess. […] According to this model, type 1 tumors are indolent neoplasms that are associated with hyperlipidemia, obesity, and signs of hyperestrogenism, such as anovulatory bleeding, infertility, late menopause, and endometrial and ovarian stromal hyperplasia. Type 2 tumors are unrelated to these features, behave aggressively, and lack the progesterone responsiveness of type 1 tumors.

• #82 Endometrial Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK525981/

  Because of this underlying pathologic mechanism, endometrial cancer is more frequently categorized by molecular subgroups based on mutation burden and copy number alterations rather than histological findings. […] The pathogenesis of non-endometrioid endometrial adenocarcinoma is related to genetic and somatic mutations and not necessarily hormonal factors. […] In low-grade endometrioid cancers, the most commonly occurring endometrial cancer type, malignant endometrial transformation results from mitogenic stimulation of EIN precursor lesions secondary to estrogenic stimulation. […] In contrast to low-grade endometrioid carcinomas, aggressive endometrial serous carcinomas, and clear cell carcinomas typically arise in atrophic, resting, or weakly proliferative endometrium through genetic mutations and epigenetic changes.

• #83

  https://link.springer.com/article/10.1007/BF02664933

  Molecular genetic evidence indicates that endometrial carcinoma likely develops as the result of a multistep process of oncogene activation and tumor suppressor gene inactivation. […] These molecular alterations appear to be specific for Type I (endometrioid) and Type II (non endometrioid) cancers. Type I cancers are characterized by mutation of PTEN, KRAS2, defects in DNA mismatch repair, as evidenced by the microsatellite instability phenotype, and a near diploid karyotype. Type II cancers often contain mutations of TP53 and Her-2/neu and are usually nondiploid. […] Furthermore, some of these tumor biomarkers constitute the targets for emerging therapies. […] Additional translational research is needed to identify molecular and genetic alterations with potential for therapeutic interventions.

• #84 Endometrial Carcinoma: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/254083-overview

  The second type occurs in women who have none of the disease states present in the classic presentation. These individuals tend to have poorly differentiated tumors, deep myometrial invasion, a high degree of metastasis to the lymph nodes and other sites, decreased sensitivity to progestins, and a poor prognosis.

• #85 Pathology of Endometrial Carcinoma | GLOWM

  https://www.glowm.com/section-view/heading/Pathology%20of%20Endometrial%20Carcinoma/item/238

  Endometrial carcinomas with associated hyperplasia tend to be well differentiated and have lesser degrees of myometrial invasion than lesions without such an association. Exogenous estrogen users have better-differentiated tumors than women who do not use estrogen. More aggressive variants of endometrial carcinoma, such as serous and clear cell carcinoma, are usually not associated with or preceded by hyperplasia. These data suggest that two classifications of endometrial carcinoma exist. One group, accounting for 65% of cases, is found in association with a high estrogen state, either endogenous or exogenous, and occurs in perimenopausal white women. This is usually a low-grade carcinoma of favorable prognosis, often accompanied by or preceded by hyperplasia, and has minimal myometrial invasion. The second type has no known predisposing conditions or any association with exogenous estrogen use or endometrial hyperplasia. These lesions are usually high-grade, aggressive neoplasms occurring in postmenopausal women, often disproportionately of Asian or African-American descent.

• #86 Pathology of Endometrial Carcinoma | GLOWM

  https://www.glowm.com/section-view/heading/Pathology%20of%20Endometrial%20Carcinoma/item/238

  Depth of myometrial invasion has proven to be an independent predictor of outcome in early-stage endometrial carcinoma. Increasing depth of myometrial invasion is associated with a greater probability of nodal metastasis and death from tumor, even when adjusted for histologic grade and subtype. Vascular invasion is an important predictor of recurrence; its presence should always be stated in the pathology report. The incidence of vascular space invasion is higher in serous and clear cell types, but it may be present in any cell type. When observed, the risk of metastasis to pelvic and para-aortic lymph nodes increases significantly. […] Provocative studies investigating hormone receptor status and genetic alterations in endometrial carcinoma have been reported recently. Expression of estrogen receptors and progesterone receptors is found in most endometrial carcinomas, but in amounts lower than can be identified in normal cycling endometrium. Although neither ER nor PR expression correlates with stage, myometrial invasion, or lymph node metastasis, many recent reports suggest that expression of PR correlates with low tumor grade, low recurrence rate, and higher survival. Conversely, the absence of PR is associated with a worse prognosis. High-grade tumors such as serous and clear cell carcinoma tend to be negative, with antibodies directed toward ER and PR. Mutations of p53 have been identified in endometrial carcinoma and hyperplasia. Inactivation of this suppressor gene occurs at a much more frequent rate in high-grade and high-stage endometrial cancers such as serous carcinoma than in well-differentiated carcinomas and hyperplasia.

• #87 Theories of Endometrial Carcinogenesis: A Multidisciplinary Approach | Modern Pathology

  https://www.nature.com/articles/3880051

  Historical observations have suggested that endometrial carcinomas vary in histopathologic appearance and clinical features. […] Specifically, studies suggest that the most common type of endometrial carcinoma, endometrioid adenocarcinoma, develops from endometrial hyperplasia in the setting of excess estrogen exposure and usually pursues an indolent clinical course. In contrast, a minority of endometrial carcinomas, best represented by serous carcinoma, do not seem to be related to estrogenic risk factors or elevated serum hormone levels, and these tumors seem to develop from atrophic rather than hyperplastic epithelium. […] We have proposed that serous carcinomas develop from endometrial intraepithelial carcinoma, a lesion representing malignant transformation of the endometrial surface epithelium.

• #88 Pathogenesis and Treatments of Endometrial Carcinoma

  https://www.imrpress.com/journal/CEOG/50/11/10.31083/j.ceog5011229/htm

  The immune checkpoints are highly expressed in the tumor microenvironment and the use of immune checkpoint inhibitors (ICIs) makes tumor cells susceptible to immune system response. The most known are the ICIs targeted against Programmed Death Ligand1 (PD-L1) and Programmed Death-1 (PD-1). Pembrolizumab is a humanized anti-PD-1 monoclonal antibody used as second-line treatment for patients with advanced MSI-H/dMMR tumors and its efficacy has been demonstrated in a phase II study KEYNOTE-158. The use of Pembrolizumab was approved in 2017 by the Food and Drug Administration (FDA) for patients suffering solid metastatic tumors, including EC. In 2019, the efficacy of Lenvatinib, which inhibits vascular endothelial growth factor receptor 1, combined with Pembrolizumab, was demonstrated by a phase II study for patients with recurrent or advanced EC, regardless of MMR status, after multiple (first or second lines) previous treatment with of platins chemotherapy. Due to strong evidence, the combined use of Pembrolizumab and Lenvatinib is the second-line currently in use for the treatment of advanced/metastatic EC after progression following platinum-based chemotherapy. Many studies on this topic are in progress. There are currently several prospective studies in progress to detect the maximum effective approach for the treatment of endometrial cancers, especially for patients with involved lymph nodes and low disease load. Studies are setting first-line ICIs, with the aim of identifying a treatment for newly diagnosed recurrent or advanced disease without chemotherapic drugs.

• #89 Pathogenesis and Treatments of Endometrial Carcinoma

  https://www.imrpress.com/journal/CEOG/50/11/10.31083/j.ceog5011229/htm

  KEYNOTE-C93/GOG-3064/ENGOT-en15 and DOMENICA trials are analyzing ICIs (Pembrolizumab and Dostarlimab) vs. chemotherapy in recurrent dMMR or advanced EC. Further trials are evaluating the use of immunotherapy-added chemotherapy. The RUBY trial (a double-blind randomized trial) aims to demonstrate the effectiveness of Dostarlimab in advanced stage or recurrent EC. The aim is to assess the safety and efficacy of Dostarlimab added to carboplatin-paclitaxel in recurrent or advanced endometrial cancer compared to chemotherapy alone. Outcomes of patients will be assessed based on proficient DNA mismatch repair (pMMR) and dMMR. Finally, with the aim of combining tumor data, the RAINBO-umbrella program is considering new molecular profile-based adjuvant therapies, specific to each subclass, as an alternative to standard post-surgical therapy in EC. For p53-mutant, the p53abn-RED will compare adjuvant chemoradiation only versus adjuvant chemoradiation and Olaparib for two years. Moreover, adjuvant pelvic external beam irradiation and Durvalumab versus adjuvant pelvic radiotherapy in MMRd EC are compared in the MMRd-GREEN trial. For no specific molecular profile EC, in the NSMP-ORANGE study, the strategy of oral progestins for two years after adjuvant pelvic external beam radiotherapy will be investigated. The last POLEmut-BLUE will evaluate the security of adjuvant therapy de-escalation in POLE-mutant EC. In the era of precision medicine, these ongoing trials may overcome current limitations in EC subclass management by obtaining a tailored adjuvant treatment guarantying effectiveness, safety, quality of life, and cost-utility.

• #90 Immune Checkpoint Inhibitors Revolutionize Endometrial Cancer Treatment

  https://www.onclive.com/view/immune-checkpoint-inhibitors-revolutionize-endometrial-cancer-treatment

  The incorporation of immune checkpoint inhibitors has altered the treatment paradigm for endometrial cancer. […] Loss of mismatch repair (MMR) proteins (MLH1, MSH2, PMS1, or MSH6) results in high microsatellite instability (MSI-H), a hallmark of Lynch syndrome. […] MMR deficient (dMMR) tumors may express PD-L1, which is the cell surface activator of the PD-1 receptor protein. When PD-1 receptors on the surface of T cells bind the PD-L1 ligand on the tumor cell, the tumor cell turns off the killing function of the T cell. However, the killing action of the T-cellspecific response can be reactivated by blocking the PD-L1 protein, or by preventing tumor cell binding at the PD-1 receptor. […] The phase 2 KEYNOTE-158 study (NCT02628067) investigated pembrolizumab in patients with dMMR or MSI-H advanced solid tumors, including endometrial cancer.

• #91 Immune Checkpoint Inhibitors Revolutionize Endometrial Cancer Treatment

  https://www.onclive.com/view/immune-checkpoint-inhibitors-revolutionize-endometrial-cancer-treatment

  A significant PFS advantage was observed in the patients with dMMR disease who received pembrolizumab (n = 112) vs placebo (n = 113); the 12-month PFS rates were 74% vs 38%, respectively. […] In the phase 3 RUBY trial (NCT03981796), dostarlimab was combined with carboplatin and paclitaxel. […] Based on findings from the RUBY trial, the FDA approved dostarlimab in combination with carboplatin and paclitaxel followed by single-agent dostarlimab in advanced or recurrent dMMR or MSI-H endometrial carcinomas. […] The use of ICIs in pMMR/microsatellite stable (MSS) endometrial carcinomas has also been investigated in recurrent endometrial cancer. […] Findings from the phase 2 expansion portion demonstrated that the ORR among all patients in the endometrial cancer cohort was 52% (95% CI, 30.6%-73.2%).

• #92 Echinacoside against Endometrial Cancer | DDDT

  https://www.dovepress.com/exploration-of-the-effect-and-potential-mechanism-of-echinacoside-agai-peer-reviewed-fulltext-article-DDDT

  Endometrial cancer (EC) is one of the most common gynecological malignancies, especially in postmenopausal women. […] However, the efficacy and the mechanism of ECH against EC have not been elucidated yet. […] A total of 110 genes were identified as potential targets of ECH against EC. […] KEGG pathway analysis showed that PI3K/Akt signaling pathways might play an important role in ECH against EC. […] The findings suggested that ECH exerted an inhibitory effect on EC cells by inhibiting the PI3K/AKT pathway. […] Based on network pharmacology, molecular docking technology and in vitro experiments, we comprehensively clarified the anti-EC efficacy of ECH through multiple targets and signal pathways. […] The PI3K-Akt signaling pathway is one of the most important signaling pathways involved in the progression of EC.

• #93 Immune Checkpoint Inhibitors Revolutionize Endometrial Cancer Treatment

  https://www.onclive.com/view/immune-checkpoint-inhibitors-revolutionize-endometrial-cancer-treatment

  A significant PFS advantage was observed in the patients with dMMR disease who received pembrolizumab (n = 112) vs placebo (n = 113); the 12-month PFS rates were 74% vs 38%, respectively. […] In the phase 3 RUBY trial (NCT03981796), dostarlimab was combined with carboplatin and paclitaxel. […] Based on findings from the RUBY trial, the FDA approved dostarlimab in combination with carboplatin and paclitaxel followed by single-agent dostarlimab in advanced or recurrent dMMR or MSI-H endometrial carcinomas. […] The use of ICIs in pMMR/microsatellite stable (MSS) endometrial carcinomas has also been investigated in recurrent endometrial cancer. […] Findings from the phase 2 expansion portion demonstrated that the ORR among all patients in the endometrial cancer cohort was 52% (95% CI, 30.6%-73.2%).

• #94 Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-AKR1C1 pathway | Oncotarget

  https://www.oncotarget.com/article/7004/

  Progestin resistance is a main obstacle for endometrial precancer/cancer conservative therapy. Therefore, biomarkers to predict progestin resistance and studies to gain a more detailed understanding of the mechanism are needed. The antioxidant Nrf2-AKR1C1 signal pathway exerts chemopreventive activity. However whether it plays a role in progestin resistance has not been explored. In this study, elevated levels of AKR1C1 and Nrf2 were found in progestin-resistant endometrial epithelia, but not in responsive endometrial glands. Exogenous overexpression of Nrf2/AKR1C1 resulted in progestin resistance. Inversely, silencing of Nrf2 or AKR1C1 rendered endometrial cancer cells more susceptible to progestin treatment. Moreover, medroxyprogesterone acetate withdrawal resulted in suppression of Nrf2/AKR1C1 expression accompanied by a reduction of cellular proliferative activity. In addition, brusatol and metformin overcame progestin resistance by down-regulating Nrf2/AKR1C1 expression. Our findings suggest that overexpression of Nrf2 and AKR1C1 in endometrial precancer/cancer may be part of the molecular mechanisms underlying progestin resistance. If validated in a larger cohort, overexpression of Nrf2 and AKR1C1 may prove to be useful biomarkers to predict progestin resistance. Targeting the Nrf2/AKR1C1 pathway may represent a new therapeutic strategy for treatment of endometrial hyperplasia/cancer.

• #95 Pathogenesis and Treatments of Endometrial Carcinoma

  https://www.imrpress.com/journal/CEOG/50/11/10.31083/j.ceog5011229/htm

  KEYNOTE-C93/GOG-3064/ENGOT-en15 and DOMENICA trials are analyzing ICIs (Pembrolizumab and Dostarlimab) vs. chemotherapy in recurrent dMMR or advanced EC. Further trials are evaluating the use of immunotherapy-added chemotherapy. The RUBY trial (a double-blind randomized trial) aims to demonstrate the effectiveness of Dostarlimab in advanced stage or recurrent EC. The aim is to assess the safety and efficacy of Dostarlimab added to carboplatin-paclitaxel in recurrent or advanced endometrial cancer compared to chemotherapy alone. Outcomes of patients will be assessed based on proficient DNA mismatch repair (pMMR) and dMMR. Finally, with the aim of combining tumor data, the RAINBO-umbrella program is considering new molecular profile-based adjuvant therapies, specific to each subclass, as an alternative to standard post-surgical therapy in EC. For p53-mutant, the p53abn-RED will compare adjuvant chemoradiation only versus adjuvant chemoradiation and Olaparib for two years. Moreover, adjuvant pelvic external beam irradiation and Durvalumab versus adjuvant pelvic radiotherapy in MMRd EC are compared in the MMRd-GREEN trial. For no specific molecular profile EC, in the NSMP-ORANGE study, the strategy of oral progestins for two years after adjuvant pelvic external beam radiotherapy will be investigated. The last POLEmut-BLUE will evaluate the security of adjuvant therapy de-escalation in POLE-mutant EC. In the era of precision medicine, these ongoing trials may overcome current limitations in EC subclass management by obtaining a tailored adjuvant treatment guarantying effectiveness, safety, quality of life, and cost-utility.

• #96 Biomolecular basis related to inflammation in the pathogenesis of endometrial cancer

  https://www.europeanreview.org/article/16038

  Endometrial cancer (EC) is a complex gynecological neoplasm with several clinical, histopathological and genetic features. Different hormonal, metabolic and biochemical axes are involved in pathogenesis. […] Indeed, inflammation is related to the pathogenesis of different tumors, including EC. […] Tumor Necrosis Factor-, Interleukin-6, Interleukin-1 Receptor Antagonist, Nuclear Factor-kB, Leptin, Adiponectin and C Reactive Protein were studied for cancer risk prediction models, risk stratification or targeted therapies. Furthermore, genetic studies evaluated the effect of inflammatory cytokines secreted by visceral adipocytes in the modulation of angiogenesis and signaling pathways such as PI3K/AKT/mTOR, that result altered in the pathogenesis of EC. […] The identification of inflammatory biomarkers released by adipose tissue, in the pathogenesis of EC, could be useful in improving diagnostic accuracy, identifying targets of therapy, suggesting useful lifestyle behaviors. A deeper knowledge of the genetic background of alterations in inflammatory pathway genes could better define the population exposed to a higher susceptibility to EC due to genetic polymorphisms. Future studies are needed to better understand this field.

• #97 Pathogenesis and Treatments of Endometrial Carcinoma

  https://www.imrpress.com/journal/CEOG/50/11/10.31083/j.ceog5011229/htm

  EC has a generally favorable prognosis. The surgical approach is the mainstay of early treatment. A tailored adjuvant therapy is necessary for selected patients, in particular for older and/or frail patients. Another important role has been recently attributed to radiomic analysis in EC risk stratification, which provides additional information. Radiomic analysis may assist in choosing the surgical treatment as demonstrated by several studies, however, additional research is needed. In addition, further studies will confirm these therapeutic products as initial standard treatment in metastatic and recurring EC. […] The aim of this editorial is to briefly summarize the new scenarios in the treatment of endometrial cancer, adding a new point of view. The approach for endometrial cancer has become increasingly personalized, and the future is to define the genetic characteristics of the tumor at the outset, in order to the guide the therapeutic strategy, accurately and less invasively.

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