HNPCC syndrome

The tumors may arise sporadically or in patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.Current experience is too limited to determine their biologic behavior and prognosis however, in one study, the patients were found to have an improved survival rate relative to those with DAs. ° Immunohistochemically, the epithelioid cells are labeled by antibodies to cytokeratins whereas trypsin, chymotrypsin, lipase, chromogranin, and synaptophysin are usually negative. CD3 antibody highlights the presence of numerous intratumoral T lymphocytes. Rare examples also contain Epstein-Barr virus RNA. ... 

Medullary carcinomas of the pancreas, like their colorectal counterparts, often show microsatellite instability, which is usually caused by somatic hypermethyl-ation of the MLHl promoter in sporadic cases " and by an inherited mutation in MLHl or MSH2 HNPCC syndrome.Immunolabeling for MLHl and MSH2 reveals loss of expression of one of these DNA mismatch repair proteins in many cases. 

PMSl). The DNA located between the nick and the mismatch is removed by 3 to 5 or 5 to 3 exonucleases depending on whether the nick is 3 or 5 to the mismatch. The gap is then filled by DNA Pol III in E. coli (Fig. 10) by DNA Pol 5 in humans and is ligated. Mismatch repair increases the spontaneous mutation rate in E. coli and yeast. Humans defective in mismatch repair exhibit a cancer-prone syndrome called hereditary nonpolyposis colon cancer (HNPCC), and sporadic mutations of mismatch repair genes are also associated with up to 50% of all human cancers (42 4). 

Inherited CRC syndromes initiate as a result of an inherited mutation in one of the genes involved in the CIN or MSI pathway. Although several CRC syndromes exist, the two most common are famUial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC), Most interestingly, tumors in FAP kindreds and tumors displaying CIN more frequently are found in the distal part of the colon, whereas tumors in HNPCC families and tumors displaying MSI more commonly occur in the proximal part of the colon. ... 

Vasen HFA, Watson P, Mecklin JP, Lynch HT and The International Collaborative Group on HNPCC. New clinical criteria for Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 1999 116 1453-6. 

Colon cancer is one of the main causes of cancer mortality in Western societies [150]. About 15-20% of colorectal tumors are causally determined by inheritance of genetic alterations such as the hereditary nonpolyposis colorectal cancer (HNPCC) and the syndrome familial adenomatous polyposis (FAP) [151,152]. Microsatellite instability, a characteristic of HNPCC, is caused by mutations in the genes essential for mismatch repair. The loss of mismatch repair has several consequences most crucially, the loss of proofreading and correction of small deletions and insertions. FAP is a rare autosomal dominant syndrome caused by an inherited mutation in the APC gene. The disease is characterized by the development of multiple colorectal adenomas, numbering from a few polyps to several thousands. 

As discussed earlier in this chapter, Lynch syndrome or hereditary nonpolyposis colon cancer syndrome (HNPCC) is a cancer predisposition syndrome caused by mutation of a mismatch repair gene. Immunohistochemistry can be used to screen for mutations in... 

Muller, A., and R. Fishel. 2002. Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC). Cancer Invest. 20 102-109. 

Inactivation of mechanisms responsible for DNA-repair This is a group of mutations affecting the ability to repair the DNA damage and include different syndromes such as HNPCC, Xeroderma pigmentosum. Ataxia telangectasia and Bloom syndrome. 

Hereditary breast-ovarian cancer syndrome (HBOC) accounts for the vast majority (85%-90%) of all hereditary ovarian cancers [5]. The site-specific ovarian cancer syndrome with only ovarian cancer accounts for 10%-15% of hereditary ovarian cancers. In hereditary nonpolyposis colorectal cancer syndrome (HNPCC), which is also known as Lynch syndrome II, patients present with colon, endometrial, breast, ovarian and other cancers [6],... 

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