Cholangiocarcinoma (Cholangiocarcinoma)  

Cholangiocarcinoma includes a group of cancers that originate in the bile ducts and is characterized by its location in relation to the liver: intrahepatic cholangiocarcinoma, the distal perihilar cholangiocarcinoma and cholangiocarcinoma.

The intrahepatic cholangiocarcinoma begins in the small bile ducts inside the liver in. This is the least common form of the disease, representing less than 10% of all cases. The perihilar cholangiocarcinoma, also known as Klatskin tumor, begins at the hilum, where the two main bile ducts entering and leaving the liver. It is the most common form of the disease, representing more than half of all cases. The remaining cases are classified as distal cholangiocarcinoma, starting in the bile ducts outside the liver. The perihilar and distal forms of the disease, sometimes grouped together and called extrahepatic cholangiocarcinoma.

The three types of cholangiocarcinoma usually cause no symptoms in its early stages, and generally this type of cancer is not diagnosed until it has already spread beyond the bile ducts to other tissues. Frequently, the symptoms manifest when bile ducts were clogged by the tumor. The most common symptom is jaundice. Other symptoms may include itching, dark urine, loss of appetite, unintentional weight loss, abdominal pain and pale and greasy stools color. These are described as "unspecific" because they can be manifestations of many different diseases. Most people who develop cholangiocarcinoma are over 65 because this cancer usually is not diagnosed until it has already spread. Affected individuals can survive for several months to several years after diagnosis.

Cancers occur when a critical accumulation of mutations in genes that control cell division, allow cells to grow and divide uncontrollably to form a tumor. In most cases cholangiocarcinoma, these genetic changes are acquired during the lifetime of a person and are only present in bile duct cells leading to tumor. Genetic changes, called somatic mutations, not inherited. They have been identified somatic mutations involved in the development of cholangiocarcinoma in many different genes. Some of these genes act as tumor suppressors. Mutations or deletions of tumor suppressor genes may allow cells to grow and divide without control or order, a hallmark of cancer. Other genes associated with cholangiocarcinoma are classified as oncogenes; when activated abnormally, these genes have the potential to cause normal cells to become cancerous. Identification of somatic mutations in cholangiocarcinoma can provide clues about how fast the cancer grows and spreads, and what treatments might be more effective. Also, they have been studied in several hereditary variations genes as potential risk factors for the development of cholangiocarcinoma. These genetic changes, which are classified as germline mutations are present in essentially all cells of the body. However, no specific changes found inherited as major risk factors for this disease.

Some of the identified genes associated with the development of cholangiocarcinoma and its location are as follows:

      • ARID1A (AT-rich domain interaction 1A) (1p35.3).
      • BAP1 (BRCA1 associated protein 1) (3p21.1).
      • BRAF (B-Raf proto-oncogene, serine / threonine kinase), (7q34).
      • FGFR2 (Fibroblast growth factor receptor 2) (10q26).
      • IDH1 (isocitrate dehydrogenase (NADP (+)) 1, cytosolic) (2q33.3).
      • IDH2 (isocitrate dehydrogenase (NADP (+)) 2, mitochondrial), (15q26.1).
      • KMT2C (lysine methyltransferase 2C) (7q36.1).
      • KRAS (KRAS proto-oncogene, GTPase) (12p12.1).
      • PBRM1 (polybromo 1), (3p21).
      • PEG3 (paternally Expressed 3) (19q13.4).
      • PTPN3 (Protein tyrosine phosphatase, non-receptor type 3), (9q31).
      • RNF43 (Ring finger protein 43) (17q22).
      • Robo2 (roundabout guidance receptor 2) (3p12.3).
      • SMAD4 (SMAD family member 4), (18q21.1).
      • TERT (telomerase reverse transcriptase), (5p15.33).
      • TP53 (tumor protein p53) (17p13.1).

They have identified several genetic risk factors not for cholangiocarcinoma. These include bile duct disease known as primary sclerosing cholangitis, stones or hepatic cysts, and exposure to certain chemical toxins used in manufacturing processes. In Southeast Asia, helminth infection staying in the bile ducts of people greatly increase the risk of developing cholangiocarcinoma. Other risk factors that have been studied include long - term infection with hepatitis B or C, cirrhosis, and chronic diseases such as irritable bowel syndrome and diabetes. In addition, it is believed that certain lifestyle factors such as smoking, alcohol consumption and obesity, can also contribute to the risk of developing cholangiocarcinoma.

Studies suggest that a combination of genetic, environmental and lifestyle factors influence a person to develop cholangiocarcinoma. However, most people who develop the disease have none of the identified risk factors.

Cholangiocarcinoma is not inherited. Studies suggest that relatives of a person with cholangiocarcinoma may have an increased risk of developing this type of cancer compared to the general population. However, most people with cholangiocarcinoma have no family history of the disease.

Tests in IVAMI: in IVAMI perform detection associated mutations concolangiocarcinoma, by complete PCR amplification of the exons of ARID1A, BAP1, BRAF, FGFR2, IDH1, IDH2, KMT2C, KRAS, PBRM1, PEG3, PTPN3, RNF43 genes , robo2, SMAD4, TERT and TP53, respectively, and subsequent sequencing.

Recommended samples: biopsy from affected tissue.