Materiały źródłowe

• #1 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  Carcinoma of unknown primary origin (CUP) is a heterogeneous group of cancers defined by the presence of metastatic disease with no identified primary tumor at presentation. […] Whether CUP is a distinct molecular genotype-phenotype relative to metastases of known cancers is unknown. […] However, whether CUP metastases are genetically and phenotypically unique remains to be determined. […] The roles of chromosomal and molecular abnormalities in CUP have been evaluated in several studies, but to date no CUP characteristics have been identified that are unique relative to those of metastases from known primary tumors. […] It has been theorized that in CUP, the angiogenic incompetence of the primary tumor leads to marked apoptosis and cell turnover, resulting in a cancer that acquires a metastatic phenotype; however, this theory cannot be clinically tested. […] The identification of specific CUP-related molecular and biochemical targets may help us identify appropriate targeted agents for individual patients with this disease.

• #2 Carcinoma of Unknown Primary (CUP): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6139-carcinoma-of-unknown-primary

  Carcinoma of unknown primary causes […] Healthcare providers diagnose carcinoma of unknown primary when they cant find the primary tumor. This can happen if the primary tumor was removed during an unrelated surgery or if tests dont detect it. […] […] Carcinoma of unknown primary (CUP) is when cancer spreads from one area of your body, but healthcare providers cant find the original cancer. Providers treat carcinoma of unknown primary based on what they learn from tests. These tests indicate the most likely type of cancer. […] […] Carcinoma of unknown primary (CUP) is when you have metastatic cancer, but healthcare providers arent sure where the cancer began. […] […] Providers use information about the primary tumor to develop treatment that targets the metastatic cancer or secondary cancer. But they can also treat carcinoma of unknown primary even when they cant find the primary tumor. Test results may give them enough information to treat CUP with specific anticancer medication.

• #3 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  Metastasis is a late event in the progression of any tumour. However, invasive cancers are occasionally detected in the form of metastatic lesions without a clearly detectable primary tumour. Cancer of unknown primary site (CUP) is defined as a confirmed metastatic tumour, with unknown primary tumour site, despite the standardized diagnostic approach that includes clinical history, routine laboratory tests, and complete physical examination. […] To date, it is unclear whether CUP is an entity with primary dormancy as its hallmark or an entity with genetic abnormalities that cause it to manifest as a primary metastatic disease. […] The debate about the clinical implications could affect the treatment choices. This raises the importance of having a biological molecule to identify the tumour. There are two hypotheses to explain the biology of CUP; one suggests that a given tumour can develop without a premalignant lesion or primary tumour; that CUP has a clear genetic and epigenetic identity and raise the need of identifying the molecular signature in the level of chromosomes.

• #4 What is Cancer of Unknown Primary? Symptoms, Risk Factors & Treatments | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/cancer-of-unknown-primary.html

  Cancer of unknown primary is a disease that has metastasized (spread) from another part of the body. The place where it began, also called the primary site, is unknown. These cases make up about 2% to 5% of cancers diagnosed in the United States. […] Because the primary site of many cancer of unknown primary cases is never found, it is difficult to say what causes them. In the cases in which the primary site is determined, possible risk factors are based on that type of cancer. […] However, it has not been proven that any of these factors make a person more likely to develop cancer of unknown primary.

• #5 Cancers of unknown primary origin: current perspectives and future therapeutic strategies | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-10-12

  It is widely accepted that systemic neoplastic spread is a late event in tumour progression. However, sometimes, rapidly invasive cancers are diagnosed because of appearance of metastatic lesions in absence of a clearly detectable primary mass. This kind of disease is referred to as cancer of unknown primary (CUP) origin and accounts for 3-5% of all cancer diagnosis. […] Although this malignant syndrome accounts for 3-5% of all cancer diagnosis, the majority of patients still lacks effective therapeutic regimens. […] There is poor consensus on the extent of diagnostic evaluations in front of metastatic cancers without a primary mass. […] The largest group of these tumours is refractory to standard chemotherapy and the median survival of CUP patients is very low. […] The overall prognosis of CUP patients is generally very poor with a median survival of 4-12 months, with about 50% of patients alive at 1 year and about 10% at 5 years from diagnosis.

• #6 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  Cancer of unknown primary (CUP) is a malignant widespread metastatic disease without an identifiable primary site after extensive clinical investigation. […] Recently, a decline is observed in the diagnosis of CUP, mainly due to improvement in detection of the primary tumors, thus decreasing the unknown primaries. […] High risk for developing CUP is seen in heavy smokers (26 or more cigarettes/day) and individuals with the lowest quartiles of waist circumference. A weak association is observed with the use of alcohol consumption and low level of education. […] Hypotheses on the pathogenesis of CUP are: 1) Stem cell producing cancer without premalignant lesion or primary cancer. 2) A very early primary cancer causes a rapid progression of metastasis. 3) Recently a possible explanation was proposed on the role of chromosomal instability contributing to aggressive disease presentation and chemoresistance.

• #7 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  Metastasis is a late event in the progression of any tumour. However, invasive cancers are occasionally detected in the form of metastatic lesions without a clearly detectable primary tumour. Cancer of unknown primary site (CUP) is defined as a confirmed metastatic tumour, with unknown primary tumour site, despite the standardized diagnostic approach that includes clinical history, routine laboratory tests, and complete physical examination. […] To date, it is unclear whether CUP is an entity with primary dormancy as its hallmark or an entity with genetic abnormalities that cause it to manifest as a primary metastatic disease. […] The debate about the clinical implications could affect the treatment choices. This raises the importance of having a biological molecule to identify the tumour. There are two hypotheses to explain the biology of CUP; one suggests that a given tumour can develop without a premalignant lesion or primary tumour; that CUP has a clear genetic and epigenetic identity and raise the need of identifying the molecular signature in the level of chromosomes.

• #8 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  Cancer of unknown primary (CUP) is a malignant widespread metastatic disease without an identifiable primary site after extensive clinical investigation. […] Recently, a decline is observed in the diagnosis of CUP, mainly due to improvement in detection of the primary tumors, thus decreasing the unknown primaries. […] High risk for developing CUP is seen in heavy smokers (26 or more cigarettes/day) and individuals with the lowest quartiles of waist circumference. A weak association is observed with the use of alcohol consumption and low level of education. […] Hypotheses on the pathogenesis of CUP are: 1) Stem cell producing cancer without premalignant lesion or primary cancer. 2) A very early primary cancer causes a rapid progression of metastasis. 3) Recently a possible explanation was proposed on the role of chromosomal instability contributing to aggressive disease presentation and chemoresistance.

• #9

  https://link.springer.com/article/10.1007/s12254-023-00935-9

  The Cancer of Unknown Primary (CUP) syndrome does not represent a single clinical entity but comprises a diverse group of malignant tumors. CUP is defined as a histologically confirmed metastatic malignant disease for which the primary tumor cannot be identified after completing initial diagnostics. […] The pathogenesis of CUPs remains elusive. Rassy et al. suggested several possible causes for CUP carcinogenesis: CUP does not undergo type 1 progression, which involves the transformation from a premalignant condition to a malignant lesion. Instead, CUP follows type 2 progression, where a malignant lesion is present at disease onset without the prior development of a nascent primary tumor. […] CUP may originate from the migration of deregulated premalignant or cancerous stem cells away from their natural tissues, leading to the formation of tumors in different locations.

• #10 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  Cancer of unknown primary (CUP) is a malignant widespread metastatic disease without an identifiable primary site after extensive clinical investigation. […] Recently, a decline is observed in the diagnosis of CUP, mainly due to improvement in detection of the primary tumors, thus decreasing the unknown primaries. […] High risk for developing CUP is seen in heavy smokers (26 or more cigarettes/day) and individuals with the lowest quartiles of waist circumference. A weak association is observed with the use of alcohol consumption and low level of education. […] Hypotheses on the pathogenesis of CUP are: 1) Stem cell producing cancer without premalignant lesion or primary cancer. 2) A very early primary cancer causes a rapid progression of metastasis. 3) Recently a possible explanation was proposed on the role of chromosomal instability contributing to aggressive disease presentation and chemoresistance.

• #11 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  The other hypothesis postulates that CUP is an artificial classification of malignant metastatic tumour, as the metastasis develops early on in the disease process, as the primary tumour and its metastases progress in parallel. […] The pathophysiological basis for CUP is still ambiguous; the origin of the primary tumour cannot be identified, even in an autopsy setting. Different hypotheses have been suggested to clarify the existence of this clinical entity. One such hypothesis considers the CUP to be an early metastatic presentation of primaries with a dominant metastatic phenotype. […] Another relevant dispute is whether the prognosis of CUP patients is linked to the prognosis of the primary tumour or a genetic profile typical to CUP. […] The metastasis-prone behaviour of CUP may be related to a functional deficiency of certain metastasis-suppressor or tumour-suppressor genes. Identifying them will help to dispel the belief that dysregulation of one or more genes and their encoded proteins pushes systemic dissemination and primary regression.

• #12 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  Cancer of unknown primary (CUP) is a malignant widespread metastatic disease without an identifiable primary site after extensive clinical investigation. […] Recently, a decline is observed in the diagnosis of CUP, mainly due to improvement in detection of the primary tumors, thus decreasing the unknown primaries. […] High risk for developing CUP is seen in heavy smokers (26 or more cigarettes/day) and individuals with the lowest quartiles of waist circumference. A weak association is observed with the use of alcohol consumption and low level of education. […] Hypotheses on the pathogenesis of CUP are: 1) Stem cell producing cancer without premalignant lesion or primary cancer. 2) A very early primary cancer causes a rapid progression of metastasis. 3) Recently a possible explanation was proposed on the role of chromosomal instability contributing to aggressive disease presentation and chemoresistance.

• #13 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #14

  https://content-dev.irisoncology.com/library/carcinoma-of-unknown-primary

  Carcinoma of unknown primary is a diagnosis healthcare professionals give when they can’t find where a cancer started. A carcinoma of unknown primary is an advanced cancer that has spread in the body. […] The cause of carcinoma of unknown primary often isn’t known. Healthcare professionals use this diagnosis when they find signs of cancer that has spread but can’t find where the cancer started. The place where a cancer started growing is called the primary cancer. […] Carcinoma of unknown primary can happen if: The primary cancer is too small to detect with imaging tests. The primary cancer was killed by the body’s immune system. The primary cancer was removed in an operation for another condition.

• #15 Carcinoma of Unknown Primary Treatment – NCI

  https://www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq

  The bodys immune system killed the primary cancer. […] The primary cancer was removed during surgery for another condition and doctors didnt know cancer had formed. […] The prognosis depends on the following: Where the cancer began in the body and where it has spread. […] The number of organs with cancer in them. […] The way the tumor cells look when viewed under a microscope. […] Whether the patient is male or female. […] Whether the cancer has just been diagnosed or has recurred (come back). […] For most patients with CUP, current treatments do not cure the cancer.

• #16 Cancer of unknown primary origin – Wikipedia

  https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin

  Because stem cells have a natural ability to migrate and also play a key role in cancer development, it has been proposed that a cancer of unknown primary site may form when deregulated, premalignant or cancerous stem cells migrate away from their natural tissue and give rise to a cancer in the new site before or without generating a tumor in their original tissue. […] CUP sometimes runs in families. It has been associated with familial lung, kidney, and colorectal cancers, which suggests that these sites may often be the origin of unidentifiable CUP cancers.

• #17 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  Gene expression profiles (GEP) have demonstrated a higher accuracy than IHC for poorly differentiated and undifferentiated carcinomas. […] The claimed accuracy of these tests to predict the primary site of CUP compared with IHC and/or autopsy ranges from 78-88.5%. […] It has been previously shown that the mutations of somatic point identified in a tumor can be utilized to identify its site of inception with restricted precision. […] The different specificities of antibodies may explain the discordance between IHC data and data obtained from the mutational analysis of genes for wild-type and mutated genes. […] The migration of stem cells (deregulated premalignant or cancerous stem cells) from their original site to other locations may give rise to cancer in new locations before or without the development of a tumour in the original tissue. […] This will be achieved by improving diagnostic methods such as IHC staining and GEP, which leads to accurate prediction of the primary site in most patients.

• #18 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/2072-6694/13/3/451

  Patients with cancer of unknown primary site suffer the burden of an uncertain disease, which is characterized by the impossibility to identify the tissue where the tumor has originated. […] The identification of the primary site of a tumor is of great importance for the patient to have access to site-specific treatments and be enrolled in clinical trials. […] Therefore, patients with cancer of unknown primary have reduced therapeutic opportunities and poor prognosis. […] The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. […] CUP origin and underlying biology remains an enigma, and different theories were developed by the scientific community about the possible origin of CUPs: some researchers suggested that CUPs originate from small undetectable, dormant, or later regressed primary lesions; others asserted that it is necessary to abandon the traditional tissue-gnostic approach and consider CUPs as early disseminating, aggressive, metastatic tumors with no existent primary site.

• #19 Metastatic Cancer With Unknown Primary Site: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/280505-overview

  In metastatic cancer, the primary site of the cancer usually dictates the treatment, expected outcome, and overall prognosis. Consequently, in patients who present with metastatic cancer without a known primary site, the search for the primary site has high priority. […] Despite the increasing sophistication in the diagnostic workup for malignancies, detailed investigations fail to reveal a primary site of origin in a minority of patients with metastatic cancer. This is often referred to as carcinoma of unknown primary origin (CUP) or occult primary malignancy. […] CUP is characterized by an aggressive course and resistance to conventional chemotherapy. […] Two main hypotheses have been proposed to explain metastatic cancer with an unknown primary (CUP). One is that a single cell escapes the controls of normal cell replication, forms a tumor at the site of origin, and the tumor cells ultimately metastasize to other organs, but the original tumor is too small to be detected at the time of metastasis.

• #20

  https://content-dev.irisoncology.com/library/carcinoma-of-unknown-primary

  Carcinoma of unknown primary is a diagnosis healthcare professionals give when they can’t find where a cancer started. A carcinoma of unknown primary is an advanced cancer that has spread in the body. […] The cause of carcinoma of unknown primary often isn’t known. Healthcare professionals use this diagnosis when they find signs of cancer that has spread but can’t find where the cancer started. The place where a cancer started growing is called the primary cancer. […] Carcinoma of unknown primary can happen if: The primary cancer is too small to detect with imaging tests. The primary cancer was killed by the body’s immune system. The primary cancer was removed in an operation for another condition.

• #21 Cancer of unknown primary

  https://www.cancervic.org.au/cancer-information/types-of-cancer/unknown-primary/cancer-of-unknown-primary.html

  Cancer of unknown primary (CUP) is when cancer cells are found in the body but the place the cancer began is not known. This means it is a secondary cancer that has spread to a new place from an unknown primary cancer somewhere else in the body. […] For most people diagnosed with cancer, the primary cancer is easy to identify. Doctors conduct tests to find out where the cancer started to grow and to see if it has spread. Sometimes, however, cancer is found in one or more secondary sites and test results cant show where the cancer began. […] Reasons why your doctors cannot find the primary cancer include: the secondary cancer has grown quickly, but the primary cancer is still too small to be seen on scans or found on tests; your immune system has destroyed the primary cancer, but not the secondary cancer; the primary cancer cant be seen on x-rays, imaging scans or endoscopies because its hidden by a secondary cancer that has grown close to or over it; the cancer may be found in many parts of the body, but it isnt clear from the scans or pathology tests which is the primary cancer.

• #22

  https://content-dev.irisoncology.com/library/carcinoma-of-unknown-primary

  Carcinoma of unknown primary is a diagnosis healthcare professionals give when they can’t find where a cancer started. A carcinoma of unknown primary is an advanced cancer that has spread in the body. […] The cause of carcinoma of unknown primary often isn’t known. Healthcare professionals use this diagnosis when they find signs of cancer that has spread but can’t find where the cancer started. The place where a cancer started growing is called the primary cancer. […] Carcinoma of unknown primary can happen if: The primary cancer is too small to detect with imaging tests. The primary cancer was killed by the body’s immune system. The primary cancer was removed in an operation for another condition.

• #23 Carcinoma of Unknown Primary Treatment – NCI

  https://www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq

  Carcinoma of unknown primary (CUP) is a rare disease in which malignant (cancer) cells are found in the body but the place the cancer began is not known. […] Sometimes the primary cancer is never found. […] Because the place where the cancer started is not known, many tests and procedures may be done to search for the primary cancer. […] When the type of cancer cells or tissue removed is different from the type of cancer cells expected to be found, a diagnosis of CUP may be made. […] Tests and procedures used to find the primary cancer depend on where the cancer has spread. […] Sometimes CUP does not cause any signs or symptoms. […] The primary cancer (the cancer that first formed) may not be found for one of the following reasons: The primary cancer is very small and grows slowly.

• #24

  https://content-dev.irisoncology.com/library/carcinoma-of-unknown-primary

  Carcinoma of unknown primary is a diagnosis healthcare professionals give when they can’t find where a cancer started. A carcinoma of unknown primary is an advanced cancer that has spread in the body. […] The cause of carcinoma of unknown primary often isn’t known. Healthcare professionals use this diagnosis when they find signs of cancer that has spread but can’t find where the cancer started. The place where a cancer started growing is called the primary cancer. […] Carcinoma of unknown primary can happen if: The primary cancer is too small to detect with imaging tests. The primary cancer was killed by the body’s immune system. The primary cancer was removed in an operation for another condition.

• #25 Carcinoma of Unknown Primary Treatment – NCI

  https://www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq

  The bodys immune system killed the primary cancer. […] The primary cancer was removed during surgery for another condition and doctors didnt know cancer had formed. […] The prognosis depends on the following: Where the cancer began in the body and where it has spread. […] The number of organs with cancer in them. […] The way the tumor cells look when viewed under a microscope. […] Whether the patient is male or female. […] Whether the cancer has just been diagnosed or has recurred (come back). […] For most patients with CUP, current treatments do not cure the cancer.

• #26

  https://content-dev.irisoncology.com/library/carcinoma-of-unknown-primary

  Carcinoma of unknown primary is a diagnosis healthcare professionals give when they can’t find where a cancer started. A carcinoma of unknown primary is an advanced cancer that has spread in the body. […] The cause of carcinoma of unknown primary often isn’t known. Healthcare professionals use this diagnosis when they find signs of cancer that has spread but can’t find where the cancer started. The place where a cancer started growing is called the primary cancer. […] Carcinoma of unknown primary can happen if: The primary cancer is too small to detect with imaging tests. The primary cancer was killed by the body’s immune system. The primary cancer was removed in an operation for another condition.

• #27 Carcinoma of Unknown Primary Treatment – NCI

  https://www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq

  The bodys immune system killed the primary cancer. […] The primary cancer was removed during surgery for another condition and doctors didnt know cancer had formed. […] The prognosis depends on the following: Where the cancer began in the body and where it has spread. […] The number of organs with cancer in them. […] The way the tumor cells look when viewed under a microscope. […] Whether the patient is male or female. […] Whether the cancer has just been diagnosed or has recurred (come back). […] For most patients with CUP, current treatments do not cure the cancer.

• #28 Cancer of unknown primary

  https://www.cancervic.org.au/cancer-information/types-of-cancer/unknown-primary/cancer-of-unknown-primary.html

  Cancer of unknown primary (CUP) is when cancer cells are found in the body but the place the cancer began is not known. This means it is a secondary cancer that has spread to a new place from an unknown primary cancer somewhere else in the body. […] For most people diagnosed with cancer, the primary cancer is easy to identify. Doctors conduct tests to find out where the cancer started to grow and to see if it has spread. Sometimes, however, cancer is found in one or more secondary sites and test results cant show where the cancer began. […] Reasons why your doctors cannot find the primary cancer include: the secondary cancer has grown quickly, but the primary cancer is still too small to be seen on scans or found on tests; your immune system has destroyed the primary cancer, but not the secondary cancer; the primary cancer cant be seen on x-rays, imaging scans or endoscopies because its hidden by a secondary cancer that has grown close to or over it; the cancer may be found in many parts of the body, but it isnt clear from the scans or pathology tests which is the primary cancer.

• #29 All About Cancer of Unknown Primary | OncoLink

  https://es.oncolink.org/tipos-de-cancer/carcinoma-de-primario-desconocido/all-about-cancer-of-unknown-primary

  Cancer can start anywhere in the body. Where the cancer starts is called the primary cancer site. […] When this happens, the cancer is called a „cancer of unknown primary” (CUP). CUP can also be called occult primary tumor. CUP is a metastatic cancer that is diagnosed with a biopsy, but it is unknown where the cancer started. […] There are a few reasons why the primary tumor may not be found: The primary cancer is very small and slow growing. The metastatic cells may grow faster or cause more symptoms than the primary tumor. The primary cancer was removed unknowingly during surgery for something else. Your immune system has already killed the primary cancer cells. […] Your provider may have other thoughts about why the primary tumor cannot be found. […] Most poorly differentiated carcinomas can be better described as melanoma, lymphoma, or sarcoma. While the primary site of these cancers may not be found, knowing this tumor classification can help with treatment decisions. […] CUP is a rare disease in which the primary site of cancer cannot be identified.

• #30 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  Gene expression profiles (GEP) have demonstrated a higher accuracy than IHC for poorly differentiated and undifferentiated carcinomas. […] The claimed accuracy of these tests to predict the primary site of CUP compared with IHC and/or autopsy ranges from 78-88.5%. […] It has been previously shown that the mutations of somatic point identified in a tumor can be utilized to identify its site of inception with restricted precision. […] The different specificities of antibodies may explain the discordance between IHC data and data obtained from the mutational analysis of genes for wild-type and mutated genes. […] The migration of stem cells (deregulated premalignant or cancerous stem cells) from their original site to other locations may give rise to cancer in new locations before or without the development of a tumour in the original tissue. […] This will be achieved by improving diagnostic methods such as IHC staining and GEP, which leads to accurate prediction of the primary site in most patients.

• #31 Cancer of Unknown Primary Risk Factors | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/causes-risks-prevention/risk-factors.html

  A risk factor is anything that affects a persons chance of getting a disease such as cancer. […] Since the exact type of cancer is not known, its hard to identify factors that might affect risk for cancer of unknown primary (CUP). […] Smoking is probably an important risk factor for CUP. More than half of patients with CUP have a history of smoking. […] Overall, however, there are no factors that specifically increase the risk of cancer of unknown primary. Even in people who may have one or more of the risk factors above, its not possible to know for sure if these factors contributed to the cancer.

• #32 Cancer of Unknown Primary | Causes, Symptoms & Treatments | Cancer Council

  https://www.cancer.org.au/cancer-information/types-of-cancer/cancer-of-unknown-primary

  Cancer of unknown primary (CUP) is the term used to describe a metastatic cancer (cancer that has spread) with an unknown starting point. […] For patients with CUP, the primary cancer site is not known, therefore it is difficult to identify risk factors. Smoking may be an important risk factor, as more than half of cancer of unknown primary patients have a history of smoking. Other risk factors may include older age, diet, alcohol and obesity – common risk factors for many cancers. […] Since the causes of CUP are unknown, there is no prevention advice specific to this disease. Having a generally healthy lifestyle – including not smoking, maintaining a healthy diet and weight and limiting alcohol consumption – may be protective.

• #33 Risk factors for cancer of unknown primary: a literature review | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-10794-6

  Cancer of Unknown Primary (CUP) is metastatic cancer with an unidentifiable primary tumour origin during life. It remains difficult to study the occurrence and aetiology of CUP. Hitherto, it is unclear whether risk factors are associated with CUP, yet identifying these factors could reveal whether CUP is a specific entity or a cluster of metastasised cancers from various primary tumour origins. There appears to be an increased risk for smoking in relation to CUP. However, limited suggestive evidence was found to link alcohol consumption, diabetes mellitus, and family history of cancer as increased risks for CUP. No conclusive associations could be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or socioeconomic status and CUP risk. This review highlights smoking, alcohol consumption, diabetes mellitus and family history of cancer as CUP risk factors. Yet, there remains insufficient epidemiological evidence to conclude that CUP has its own specific risk factor profile.

• #34 Cancer of Unknown Primary Risk Factors | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/causes-risks-prevention/risk-factors.html

  A risk factor is anything that affects a persons chance of getting a disease such as cancer. […] Since the exact type of cancer is not known, its hard to identify factors that might affect risk for cancer of unknown primary (CUP). […] Smoking is probably an important risk factor for CUP. More than half of patients with CUP have a history of smoking. […] Overall, however, there are no factors that specifically increase the risk of cancer of unknown primary. Even in people who may have one or more of the risk factors above, its not possible to know for sure if these factors contributed to the cancer.

• #35 Cancer of Unknown Primary | Causes, Symptoms & Treatments | Cancer Council

  https://www.cancer.org.au/cancer-information/types-of-cancer/cancer-of-unknown-primary

  Cancer of unknown primary (CUP) is the term used to describe a metastatic cancer (cancer that has spread) with an unknown starting point. […] For patients with CUP, the primary cancer site is not known, therefore it is difficult to identify risk factors. Smoking may be an important risk factor, as more than half of cancer of unknown primary patients have a history of smoking. Other risk factors may include older age, diet, alcohol and obesity – common risk factors for many cancers. […] Since the causes of CUP are unknown, there is no prevention advice specific to this disease. Having a generally healthy lifestyle – including not smoking, maintaining a healthy diet and weight and limiting alcohol consumption – may be protective.

• #36 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  Cancer of unknown primary (CUP) is a malignant widespread metastatic disease without an identifiable primary site after extensive clinical investigation. […] Recently, a decline is observed in the diagnosis of CUP, mainly due to improvement in detection of the primary tumors, thus decreasing the unknown primaries. […] High risk for developing CUP is seen in heavy smokers (26 or more cigarettes/day) and individuals with the lowest quartiles of waist circumference. A weak association is observed with the use of alcohol consumption and low level of education. […] Hypotheses on the pathogenesis of CUP are: 1) Stem cell producing cancer without premalignant lesion or primary cancer. 2) A very early primary cancer causes a rapid progression of metastasis. 3) Recently a possible explanation was proposed on the role of chromosomal instability contributing to aggressive disease presentation and chemoresistance.

• #37 Cancer of unknown primary site

  https://www.racgp.org.au/afp/2015/september/cancer-of-unknown-primary-site

  Cancer of unknown primary (CUP) is the diagnosis given to patients with metastatic cancer with no known site of origin. […] Smoking is the only identified risk factor. […] Evidence from a single prospective cohort study suggests that heavy smoking is associated with an increased risk of CUP (about 4-fold), and high alcohol consumption and wide waist circumference may also increase risk. […] However, this analysis included all CUP subtypes, potentially masking aetiologically relevant associations for the minority subtypes, confirmed and provisional CUP. […] The strongest risk factor is age: CUP is vanishingly rare in people under the age of 40 years and in Australia in 2011 the average age at diagnosis was 75 years. […] Surprisingly, little is known about lifestyle and other risk factors for CUP.

• #38 What is cancer of unknown primary (CUP)? | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/cancer-unknown-primary-cup/about

  Cancer of unknown primary (CUP) means that cancer spread (secondary cancer) has been found in your body, but doctors don’t know where the cancer started (the primary cancer). […] Sometimes secondary cancers are found in one or more parts of the body, but despite several tests, doctors can’t find the primary tumour. If tests show that you have a cancer that has spread, but your doctors cant find the primary tumour, its called a malignancy of unknown primary origin (MUO). […] The most common places for secondary cancers to be found are the lungs, liver, bones, lymph nodes, and skin. […] Most cancers are cancers of the epithelial cells. Epithelial cells are found in the skin or tissues that line or cover the internal organs. Cancers that start in epithelial tissue are called carcinomas. Most cancers of unknown primary are types of carcinoma. […] Cancer of unknown primary can develop at any age. But almost 60 out of 100 cases (almost 60%) are in people over the age of 75. […] There is no staging system for cancer of unknown primary (CUP). Doctors can group CUP by the type of cell the cancer started in.

• #39 Cancer of unknown primary site

  https://www.racgp.org.au/afp/2015/september/cancer-of-unknown-primary-site

  Cancer of unknown primary (CUP) is the diagnosis given to patients with metastatic cancer with no known site of origin. […] Smoking is the only identified risk factor. […] Evidence from a single prospective cohort study suggests that heavy smoking is associated with an increased risk of CUP (about 4-fold), and high alcohol consumption and wide waist circumference may also increase risk. […] However, this analysis included all CUP subtypes, potentially masking aetiologically relevant associations for the minority subtypes, confirmed and provisional CUP. […] The strongest risk factor is age: CUP is vanishingly rare in people under the age of 40 years and in Australia in 2011 the average age at diagnosis was 75 years. […] Surprisingly, little is known about lifestyle and other risk factors for CUP.

• #40 Risk factors for cancer of unknown primary: a literature review | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-10794-6

  Cancer of Unknown Primary (CUP) is metastatic cancer with an unidentifiable primary tumour origin during life. It remains difficult to study the occurrence and aetiology of CUP. Hitherto, it is unclear whether risk factors are associated with CUP, yet identifying these factors could reveal whether CUP is a specific entity or a cluster of metastasised cancers from various primary tumour origins. There appears to be an increased risk for smoking in relation to CUP. However, limited suggestive evidence was found to link alcohol consumption, diabetes mellitus, and family history of cancer as increased risks for CUP. No conclusive associations could be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or socioeconomic status and CUP risk. This review highlights smoking, alcohol consumption, diabetes mellitus and family history of cancer as CUP risk factors. Yet, there remains insufficient epidemiological evidence to conclude that CUP has its own specific risk factor profile.

• #41 Risk factors for cancer of unknown primary: a literature review | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-10794-6

  Based on epidemiological evidence from 4 casecontrol and 14 cohort studies reviewed here, there is an association between smoking and CUP risk, but evidence for alcohol consumption, DM, and FHC is limited suggestive. The evidence does not allow conclusive associations to be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or SES. […] This literature review examined various factors and showed that smoking, alcohol consumption, DM, and FHC appear to be associated with CUP risk. The heterogeneous nature of CUP as well as the lack of a specific aetiology suggest that CUP is not a specific entity. Indeed, it is more likely that CUP is a cluster of metastasised cancers, which would explain the variation in both aetiology and immunology.

• #42 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  Cancer of unknown primary (CUP) is a malignant widespread metastatic disease without an identifiable primary site after extensive clinical investigation. […] Recently, a decline is observed in the diagnosis of CUP, mainly due to improvement in detection of the primary tumors, thus decreasing the unknown primaries. […] High risk for developing CUP is seen in heavy smokers (26 or more cigarettes/day) and individuals with the lowest quartiles of waist circumference. A weak association is observed with the use of alcohol consumption and low level of education. […] Hypotheses on the pathogenesis of CUP are: 1) Stem cell producing cancer without premalignant lesion or primary cancer. 2) A very early primary cancer causes a rapid progression of metastasis. 3) Recently a possible explanation was proposed on the role of chromosomal instability contributing to aggressive disease presentation and chemoresistance.

• #43 Risk factors for cancer of unknown primary: a literature review | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-10794-6

  Cancer of Unknown Primary (CUP) is metastatic cancer with an unidentifiable primary tumour origin during life. It remains difficult to study the occurrence and aetiology of CUP. Hitherto, it is unclear whether risk factors are associated with CUP, yet identifying these factors could reveal whether CUP is a specific entity or a cluster of metastasised cancers from various primary tumour origins. There appears to be an increased risk for smoking in relation to CUP. However, limited suggestive evidence was found to link alcohol consumption, diabetes mellitus, and family history of cancer as increased risks for CUP. No conclusive associations could be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or socioeconomic status and CUP risk. This review highlights smoking, alcohol consumption, diabetes mellitus and family history of cancer as CUP risk factors. Yet, there remains insufficient epidemiological evidence to conclude that CUP has its own specific risk factor profile.

• #44 Risk factors for cancer of unknown primary: a literature review | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-10794-6

  Cancer of Unknown Primary (CUP) is metastatic cancer with an unidentifiable primary tumour origin during life. It remains difficult to study the occurrence and aetiology of CUP. Hitherto, it is unclear whether risk factors are associated with CUP, yet identifying these factors could reveal whether CUP is a specific entity or a cluster of metastasised cancers from various primary tumour origins. There appears to be an increased risk for smoking in relation to CUP. However, limited suggestive evidence was found to link alcohol consumption, diabetes mellitus, and family history of cancer as increased risks for CUP. No conclusive associations could be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or socioeconomic status and CUP risk. This review highlights smoking, alcohol consumption, diabetes mellitus and family history of cancer as CUP risk factors. Yet, there remains insufficient epidemiological evidence to conclude that CUP has its own specific risk factor profile.

• #45 CUP Syndrome (Cancer of Unknown Primary) | Medically Roche

  https://medically.roche.com/global/en/microsites/about-cup-syndrome/cup-syndrome.html

  CUP (cancer of unknown primary) syndrome is defined as a histologically and clinically verified cancer for which only metastases can be found at the time of diagnosis, but no primary tumour is detectable. […] There are various hypotheses on aetiology and pathogenesis. One tentative explanation for CUP is the stem cell theory of cancer. Asynchronous division of the premalignantly or malignantly transformed stem cells may produce daughter cells that do not grow locally but are able to metastasise. Given the favourable microenvironment of these metastases, these may spread to another site, even though no tumour develops in the tissue of origin. This hypothesis is supported by tumour genomics, with clonal evolution documented in various cancers (e.g., lung cancer). […] Potential risk factors that support the development of CUP syndrome include: Diabetes mellitus, Smoking, Obesity, A positive family history of cancer.

• #46 Cancer of unknown primary origin – Wikipedia

  https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin

  Because stem cells have a natural ability to migrate and also play a key role in cancer development, it has been proposed that a cancer of unknown primary site may form when deregulated, premalignant or cancerous stem cells migrate away from their natural tissue and give rise to a cancer in the new site before or without generating a tumor in their original tissue. […] CUP sometimes runs in families. It has been associated with familial lung, kidney, and colorectal cancers, which suggests that these sites may often be the origin of unidentifiable CUP cancers.

• #47 Risk factors for cancer of unknown primary: a literature review | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-10794-6

  Cancer of Unknown Primary (CUP) is metastatic cancer with an unidentifiable primary tumour origin during life. It remains difficult to study the occurrence and aetiology of CUP. Hitherto, it is unclear whether risk factors are associated with CUP, yet identifying these factors could reveal whether CUP is a specific entity or a cluster of metastasised cancers from various primary tumour origins. There appears to be an increased risk for smoking in relation to CUP. However, limited suggestive evidence was found to link alcohol consumption, diabetes mellitus, and family history of cancer as increased risks for CUP. No conclusive associations could be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or socioeconomic status and CUP risk. This review highlights smoking, alcohol consumption, diabetes mellitus and family history of cancer as CUP risk factors. Yet, there remains insufficient epidemiological evidence to conclude that CUP has its own specific risk factor profile.

• #48 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/2072-6694/13/3/451

  Patients with cancer of unknown primary site suffer the burden of an uncertain disease, which is characterized by the impossibility to identify the tissue where the tumor has originated. […] The identification of the primary site of a tumor is of great importance for the patient to have access to site-specific treatments and be enrolled in clinical trials. […] Therefore, patients with cancer of unknown primary have reduced therapeutic opportunities and poor prognosis. […] The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. […] CUP origin and underlying biology remains an enigma, and different theories were developed by the scientific community about the possible origin of CUPs: some researchers suggested that CUPs originate from small undetectable, dormant, or later regressed primary lesions; others asserted that it is necessary to abandon the traditional tissue-gnostic approach and consider CUPs as early disseminating, aggressive, metastatic tumors with no existent primary site.

• #49 HPV-Related Retroperitoneal Squamous Cell Carcinoma of Unknown Primary: A Case Report

  https://www.e-crt.org/journal/view.php?number=2397

  A 56-year-old female was referred to our hospital due to a mass measuring 5 cm in size in the left pelvic cavity, which was found incidentally during a health examination by ultrasonography. […] Even after further studies, we did not find any other primary lesion. […] Retroperitoneal squamous cell carcinoma of unknown primary is extremely rare and little is known about it. It is reported that HPV may be associated with the disease. […] To the best of our knowledge, the case presented here is the first description of a primary retroperitoneal SCC with the positivity of HPV 18 in South Korea. Currently, FDG-PET is one of the preferred imaging modalities used in detection of carcinoma of unknown primary origin. […] HPV may be associated with pelvic masses of unknown primary, even in patients with normal cervical examination results. Hence, the result of HPV test could have an impact on finding suspicious primary lesion and treatment modality in our case.

• #50 Cancer of Unknown Primary | Causes, Symptoms & Treatments | Cancer Council

  https://www.cancer.org.au/cancer-information/types-of-cancer/cancer-of-unknown-primary

  Cancer of unknown primary (CUP) is the term used to describe a metastatic cancer (cancer that has spread) with an unknown starting point. […] For patients with CUP, the primary cancer site is not known, therefore it is difficult to identify risk factors. Smoking may be an important risk factor, as more than half of cancer of unknown primary patients have a history of smoking. Other risk factors may include older age, diet, alcohol and obesity – common risk factors for many cancers. […] Since the causes of CUP are unknown, there is no prevention advice specific to this disease. Having a generally healthy lifestyle – including not smoking, maintaining a healthy diet and weight and limiting alcohol consumption – may be protective.

• #51 Cancer of unknown primary site

  https://www.racgp.org.au/afp/2015/september/cancer-of-unknown-primary-site

  Cancer of unknown primary (CUP) is the diagnosis given to patients with metastatic cancer with no known site of origin. […] Smoking is the only identified risk factor. […] Evidence from a single prospective cohort study suggests that heavy smoking is associated with an increased risk of CUP (about 4-fold), and high alcohol consumption and wide waist circumference may also increase risk. […] However, this analysis included all CUP subtypes, potentially masking aetiologically relevant associations for the minority subtypes, confirmed and provisional CUP. […] The strongest risk factor is age: CUP is vanishingly rare in people under the age of 40 years and in Australia in 2011 the average age at diagnosis was 75 years. […] Surprisingly, little is known about lifestyle and other risk factors for CUP.

• #52 Risk factors for cancer of unknown primary: a literature review | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-10794-6

  Based on epidemiological evidence from 4 casecontrol and 14 cohort studies reviewed here, there is an association between smoking and CUP risk, but evidence for alcohol consumption, DM, and FHC is limited suggestive. The evidence does not allow conclusive associations to be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or SES. […] This literature review examined various factors and showed that smoking, alcohol consumption, DM, and FHC appear to be associated with CUP risk. The heterogeneous nature of CUP as well as the lack of a specific aetiology suggest that CUP is not a specific entity. Indeed, it is more likely that CUP is a cluster of metastasised cancers, which would explain the variation in both aetiology and immunology.

• #53 Cancers of unknown primary origin: current perspectives and future therapeutic strategies | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-10-12

  However in case of CUP diagnosis, therapy regimes lack to be specific and, in the vast majority of cases, chemotherapy regimens include platinum, an alkylating agent which is effectively used for the management of patients with the most common solid tumors. […] Despite the large number of patients diagnosed with carcinoma of unknown primary site of origin, innovative and individualized approaches to managing these patients have lagged behind many other solid tumors. […] Several methods for identifying CUP samples based on their gene expression profiles have been developed. […] This approach will lead to the creation of a new sensitive platform that might select an otherwise heterogeneous group of patients, such as that of patients presenting with metastatic cancers of unknown primary site of origin.

• #54 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Cancer-of-Unknown-Primary.aspx

  CUP comprises many types of cancers, where each one is caused due to a variety of reasons; hence, it is very difficult to state a specific cause for CUP. […] Cancer is actually caused because of a genetic change in the DNA of a cell, with each cell consisting of a DNA molecule that provides genetic information and instructions for cell growth and its functions. There are particular genes to regulate cell functions like their growth, multiplication, and death. The genes that boost cell division and increase the lifespan of cells are termed oncogenes, and those that decelerate the cell division and assassinate the cells at a specific situation are known as tumor suppressor genes. Genetic mutations in these genes can cause cancer. However, cancer does not occur due to a single mutation, but requires multiple numbers of genetic changes.

• #55 Carcinoma of unknown primary origin (CUP) | EBSCO Research Starters

  https://www.ebsco.com/research-starters/health-and-medicine/carcinoma-unknown-primary-origin-cup

  Additionally, many carcinomas are the result of a random genetic mutation, resulting in abnormally formed cells that can be cancerous. […] The origin of carcinoma is in the cells of the epithelium, which lines both the outside (skin) and the inside cavities and lumen of tissues and organs. […] Over 90 percent of all diagnosed cancers are a result of carcinoma. Of those, from 2 to 5 percent are carcinomas of unknown origin, which have metastasized from an unknown location. […] Cancer is determined to be carcinoma of unknown primary origin when there is no evidence to determine the origin of the cancerous cells. […] Research has shown that over half of patients with carcinoma of unknown primary origin have cancer that originated in the lung or pancreas. […] The prognosis for patients with carcinoma of unknown primary origin is poor. […] In the 2020s, immunotherapies are showing great promise to include in treatments for carcinomas of unknown origins.

• #56 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Cancer-of-Unknown-Primary.aspx

  CUP comprises many types of cancers, where each one is caused due to a variety of reasons; hence, it is very difficult to state a specific cause for CUP. […] Cancer is actually caused because of a genetic change in the DNA of a cell, with each cell consisting of a DNA molecule that provides genetic information and instructions for cell growth and its functions. There are particular genes to regulate cell functions like their growth, multiplication, and death. The genes that boost cell division and increase the lifespan of cells are termed oncogenes, and those that decelerate the cell division and assassinate the cells at a specific situation are known as tumor suppressor genes. Genetic mutations in these genes can cause cancer. However, cancer does not occur due to a single mutation, but requires multiple numbers of genetic changes.

• #57 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Cancer-of-Unknown-Primary.aspx

  CUP comprises many types of cancers, where each one is caused due to a variety of reasons; hence, it is very difficult to state a specific cause for CUP. […] Cancer is actually caused because of a genetic change in the DNA of a cell, with each cell consisting of a DNA molecule that provides genetic information and instructions for cell growth and its functions. There are particular genes to regulate cell functions like their growth, multiplication, and death. The genes that boost cell division and increase the lifespan of cells are termed oncogenes, and those that decelerate the cell division and assassinate the cells at a specific situation are known as tumor suppressor genes. Genetic mutations in these genes can cause cancer. However, cancer does not occur due to a single mutation, but requires multiple numbers of genetic changes.

• #58 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Cancer-of-Unknown-Primary.aspx

  CUP comprises many types of cancers, where each one is caused due to a variety of reasons; hence, it is very difficult to state a specific cause for CUP. […] Cancer is actually caused because of a genetic change in the DNA of a cell, with each cell consisting of a DNA molecule that provides genetic information and instructions for cell growth and its functions. There are particular genes to regulate cell functions like their growth, multiplication, and death. The genes that boost cell division and increase the lifespan of cells are termed oncogenes, and those that decelerate the cell division and assassinate the cells at a specific situation are known as tumor suppressor genes. Genetic mutations in these genes can cause cancer. However, cancer does not occur due to a single mutation, but requires multiple numbers of genetic changes.

• #59 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  These basic hypotheses have not been confirmed because studies conducted to date have yielded neither consistent nor specific gene/protein abnormalities 'pivotal’ to the development and survival of CUP. […] CUP is considered to be an aggressive metastatic disease, but it is not known whether the prognosis is different from the metastatic cancers of known primary site. […] The aggressive behaviour of CUP may be due to initial immunosuppression, which may lead to mutation accumulation. […] Although the primary tumour in CUP is thought to be dormant, CUP patients have early distant metastases. […] The metastatic tendency may explain poor prognosis, and metastasis is considered to be the cause of death in most patients with primary cancers. […] Metastasis involves several genes, and it has been shown that some essential metastatic genes are overexpressed in CUP: vessel endothelial growth factor, and matrix metalloproteinases, proteolytic enzymes that mediate local invasion and metastasis.

• #60 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  Carcinoma of unknown primary origin (CUP) is a heterogeneous group of cancers defined by the presence of metastatic disease with no identified primary tumor at presentation. […] Whether CUP is a distinct molecular genotype-phenotype relative to metastases of known cancers is unknown. […] However, whether CUP metastases are genetically and phenotypically unique remains to be determined. […] The roles of chromosomal and molecular abnormalities in CUP have been evaluated in several studies, but to date no CUP characteristics have been identified that are unique relative to those of metastases from known primary tumors. […] It has been theorized that in CUP, the angiogenic incompetence of the primary tumor leads to marked apoptosis and cell turnover, resulting in a cancer that acquires a metastatic phenotype; however, this theory cannot be clinically tested. […] The identification of specific CUP-related molecular and biochemical targets may help us identify appropriate targeted agents for individual patients with this disease.

• #61 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #62 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #63 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #64 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #65 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  These basic hypotheses have not been confirmed because studies conducted to date have yielded neither consistent nor specific gene/protein abnormalities 'pivotal’ to the development and survival of CUP. […] CUP is considered to be an aggressive metastatic disease, but it is not known whether the prognosis is different from the metastatic cancers of known primary site. […] The aggressive behaviour of CUP may be due to initial immunosuppression, which may lead to mutation accumulation. […] Although the primary tumour in CUP is thought to be dormant, CUP patients have early distant metastases. […] The metastatic tendency may explain poor prognosis, and metastasis is considered to be the cause of death in most patients with primary cancers. […] Metastasis involves several genes, and it has been shown that some essential metastatic genes are overexpressed in CUP: vessel endothelial growth factor, and matrix metalloproteinases, proteolytic enzymes that mediate local invasion and metastasis.

• #66 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  These basic hypotheses have not been confirmed because studies conducted to date have yielded neither consistent nor specific gene/protein abnormalities 'pivotal’ to the development and survival of CUP. […] CUP is considered to be an aggressive metastatic disease, but it is not known whether the prognosis is different from the metastatic cancers of known primary site. […] The aggressive behaviour of CUP may be due to initial immunosuppression, which may lead to mutation accumulation. […] Although the primary tumour in CUP is thought to be dormant, CUP patients have early distant metastases. […] The metastatic tendency may explain poor prognosis, and metastasis is considered to be the cause of death in most patients with primary cancers. […] Metastasis involves several genes, and it has been shown that some essential metastatic genes are overexpressed in CUP: vessel endothelial growth factor, and matrix metalloproteinases, proteolytic enzymes that mediate local invasion and metastasis.

• #67 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  These basic hypotheses have not been confirmed because studies conducted to date have yielded neither consistent nor specific gene/protein abnormalities 'pivotal’ to the development and survival of CUP. […] CUP is considered to be an aggressive metastatic disease, but it is not known whether the prognosis is different from the metastatic cancers of known primary site. […] The aggressive behaviour of CUP may be due to initial immunosuppression, which may lead to mutation accumulation. […] Although the primary tumour in CUP is thought to be dormant, CUP patients have early distant metastases. […] The metastatic tendency may explain poor prognosis, and metastasis is considered to be the cause of death in most patients with primary cancers. […] Metastasis involves several genes, and it has been shown that some essential metastatic genes are overexpressed in CUP: vessel endothelial growth factor, and matrix metalloproteinases, proteolytic enzymes that mediate local invasion and metastasis.

• #68 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  The pattern of CUP spread at diagnosis may provide indications as to whether the primary site is above or below the diaphragm. […] The pattern of carcinoma metastases presented as CUP may be considerably different from that predicted from the usual presentation. […] A CUP diagnosis is often reached when the patient has a histologically confirmed metastatic cancer with unidentifiable primary tumor site, despite the standard diagnostic approach. […] It is believed that identifying the site of primary tumour will improve the customization of therapy, results in improvement of the patient’s survival rate. […] The major limitation of IHC staining is that IHC is not useful in the case of poorly differentiated cancers in addition to the inability to get an adequate biopsy sample and the variable interpretation by different pathologists.

• #69 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  The pattern of CUP spread at diagnosis may provide indications as to whether the primary site is above or below the diaphragm. […] The pattern of carcinoma metastases presented as CUP may be considerably different from that predicted from the usual presentation. […] A CUP diagnosis is often reached when the patient has a histologically confirmed metastatic cancer with unidentifiable primary tumor site, despite the standard diagnostic approach. […] It is believed that identifying the site of primary tumour will improve the customization of therapy, results in improvement of the patient’s survival rate. […] The major limitation of IHC staining is that IHC is not useful in the case of poorly differentiated cancers in addition to the inability to get an adequate biopsy sample and the variable interpretation by different pathologists.

• #70 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #71 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #72 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #73 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #74 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #75 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  The pattern of CUP spread at diagnosis may provide indications as to whether the primary site is above or below the diaphragm. […] The pattern of carcinoma metastases presented as CUP may be considerably different from that predicted from the usual presentation. […] A CUP diagnosis is often reached when the patient has a histologically confirmed metastatic cancer with unidentifiable primary tumor site, despite the standard diagnostic approach. […] It is believed that identifying the site of primary tumour will improve the customization of therapy, results in improvement of the patient’s survival rate. […] The major limitation of IHC staining is that IHC is not useful in the case of poorly differentiated cancers in addition to the inability to get an adequate biopsy sample and the variable interpretation by different pathologists.

• #76 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  Gene expression profiles (GEP) have demonstrated a higher accuracy than IHC for poorly differentiated and undifferentiated carcinomas. […] The claimed accuracy of these tests to predict the primary site of CUP compared with IHC and/or autopsy ranges from 78-88.5%. […] It has been previously shown that the mutations of somatic point identified in a tumor can be utilized to identify its site of inception with restricted precision. […] The different specificities of antibodies may explain the discordance between IHC data and data obtained from the mutational analysis of genes for wild-type and mutated genes. […] The migration of stem cells (deregulated premalignant or cancerous stem cells) from their original site to other locations may give rise to cancer in new locations before or without the development of a tumour in the original tissue. […] This will be achieved by improving diagnostic methods such as IHC staining and GEP, which leads to accurate prediction of the primary site in most patients.

• #77 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/resolver?pii=cancers13030451

  However, when post-mortem autopsies were investigated, a primary site was discovered in 70% of CUP cases, with the lung and pancreas as the most frequently detected organs of origin. […] The hypothesis of a “familial CUP” syndrome is also a matter of debate. […] Other risk factors identified so far include smoking habits and human papillomavirus (HPV) infection for squamous cell CUPs. […] In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. […] Despite the high accuracy rates achieved by GEP assays, these tools are hindered by the low quality of RNA usually obtained from FFPE samples. […] The urgent need to improve CUP diagnostic workup, paired with the critical health conditions of patients at the time of diagnosis, have led researchers to investigate the possibility to obtain information with less invasive procedures. […] Liquid biopsy aims at analyzing tumor-derived components, e.g., circulating tumor cells (CTC) or circulating tumor DNA (ctDNA), in blood or other biological fluids, thus overcoming the many limits of conventional tissue biopsy.

• #78 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #79 Cancers of unknown primary origin: current perspectives and future therapeutic strategies | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-10-12

  However in case of CUP diagnosis, therapy regimes lack to be specific and, in the vast majority of cases, chemotherapy regimens include platinum, an alkylating agent which is effectively used for the management of patients with the most common solid tumors. […] Despite the large number of patients diagnosed with carcinoma of unknown primary site of origin, innovative and individualized approaches to managing these patients have lagged behind many other solid tumors. […] Several methods for identifying CUP samples based on their gene expression profiles have been developed. […] This approach will lead to the creation of a new sensitive platform that might select an otherwise heterogeneous group of patients, such as that of patients presenting with metastatic cancers of unknown primary site of origin.

• #80 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/resolver?pii=cancers13030451

  However, when post-mortem autopsies were investigated, a primary site was discovered in 70% of CUP cases, with the lung and pancreas as the most frequently detected organs of origin. […] The hypothesis of a “familial CUP” syndrome is also a matter of debate. […] Other risk factors identified so far include smoking habits and human papillomavirus (HPV) infection for squamous cell CUPs. […] In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. […] Despite the high accuracy rates achieved by GEP assays, these tools are hindered by the low quality of RNA usually obtained from FFPE samples. […] The urgent need to improve CUP diagnostic workup, paired with the critical health conditions of patients at the time of diagnosis, have led researchers to investigate the possibility to obtain information with less invasive procedures. […] Liquid biopsy aims at analyzing tumor-derived components, e.g., circulating tumor cells (CTC) or circulating tumor DNA (ctDNA), in blood or other biological fluids, thus overcoming the many limits of conventional tissue biopsy.

• #81 What is cancer of the unknown primary (CUP)? | MD Anderson Cancer Center

  https://www.mdanderson.org/cancerwise/6-questions-about-cancer-of-the-unknown-primary.h00-159460056.html

  Cancer of the unknown primary is a rare group of metastatic cancers that are found after theyve spread, but the location of the original tumor isnt clear. […] Another idea is that the immune system or other mechanisms within the body destroyed the primary tumor on its own. […] We cant prove that hypothesis without knowing the true original location of the primary tumor, but its what I personally feel is going on with many of these patients. […] The biggest challenge that were working to overcome is determining accurate prognoses. […] We also emphasize molecular profiling, which allows us to identify biomarkers that open the door to targeted therapies and even immunotherapy.

• #82 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #83 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  Carcinoma of unknown primary origin (CUP) is a heterogeneous group of cancers defined by the presence of metastatic disease with no identified primary tumor at presentation. […] Whether CUP is a distinct molecular genotype-phenotype relative to metastases of known cancers is unknown. […] However, whether CUP metastases are genetically and phenotypically unique remains to be determined. […] The roles of chromosomal and molecular abnormalities in CUP have been evaluated in several studies, but to date no CUP characteristics have been identified that are unique relative to those of metastases from known primary tumors. […] It has been theorized that in CUP, the angiogenic incompetence of the primary tumor leads to marked apoptosis and cell turnover, resulting in a cancer that acquires a metastatic phenotype; however, this theory cannot be clinically tested. […] The identification of specific CUP-related molecular and biochemical targets may help us identify appropriate targeted agents for individual patients with this disease.

• #84 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #85 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #86 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #87 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #88 Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6820325/

  In the past 50 years, the incidence of CUP has increased probably due to higher diagnostic sensitivity, thus finding more metastatic disease. […] The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. […] The possible explanation for CUP’s aggressive behavior, drug resistance, and poor prognosis is chromosomal instability. […] The diagnosis and treatment of CUP are challenging due to its late presentation, difficulty in diagnosis, and therapeutic resistance as compared to other malignancies. […] The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site. […] Additional studies on CUP are necessary in the future to understand the disease more clearly and to answer the following questions regarding CUP. Why CUP patients do not present early in the course of the disease?, what are the risk factors in the development of CUP?, why CUP patients remain asymptomatic for a longer duration? and how effective can targeted molecular therapy be in decreasing the mortality and improving the survival period?

• #89 Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

  https://www.jcancer.org/v11p3919.htm

  Gene expression profiles (GEP) have demonstrated a higher accuracy than IHC for poorly differentiated and undifferentiated carcinomas. […] The claimed accuracy of these tests to predict the primary site of CUP compared with IHC and/or autopsy ranges from 78-88.5%. […] It has been previously shown that the mutations of somatic point identified in a tumor can be utilized to identify its site of inception with restricted precision. […] The different specificities of antibodies may explain the discordance between IHC data and data obtained from the mutational analysis of genes for wild-type and mutated genes. […] The migration of stem cells (deregulated premalignant or cancerous stem cells) from their original site to other locations may give rise to cancer in new locations before or without the development of a tumour in the original tissue. […] This will be achieved by improving diagnostic methods such as IHC staining and GEP, which leads to accurate prediction of the primary site in most patients.

• #90 Management of lymph node metastases from an unknown primary site to the head and neck (Review)

  https://www.spandidos-publications.com/10.3892/mco.2014.361

  Cancer of unknown primary site (CUP) is an intriguing clinical phenomenon found in ~39% of all head and neck cancers. It has not yet been determined whether CUP forms a distinct biological entity with specific genetic and phenotypic characteristics, or whether it is the clinical presentation of metastasis in patients with an undetected primary tumor and no visible clinical signs. […] The optimal therapeutic management of patients with CUP remains controversial, due to the absence of randomized studies comparing different treatment options. Therefore, treatment is mainly based on non-randomized evidence and institutional policy. […] There remains the question of whether CUP is different from tumors of known primary site. If we accept the concept of a specific natural history and biology of unknown primary tumors, further research on the biology of CUP should focus on determining whether this group of tumors share unique genetic, chromosomal and/or phenotypic anomalies. […] Insights into the molecular biology of CUP are required in order to identify the cell signalling pathways responsible for primary tumor dormancy and early metastatic spread, leading to the optimal diagnostic and therapeutic management of these patients.

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