胃腸および消化器系

抽象的な

Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)

Jaime Ruiz-Tovar, Antonio Arroyo and Rafael Calpena

Colorectal cancer (CRC) is the 3rd leading cause of cancer-related death in Western countries. Between 3-8% of CRC appear as hereditary forms, being the Lynch syndrome (hereditary nonpolyposis colorectal cancer) the most frequent one. The main features of Lynch syndrome are the presentation at young ages (mean 45 years), the preferent arisal in right colon (70% of the cases), the high incidence of synchronic (10%) and metachronic (30-50%) colorectal tumors, and the association with extra colonic neoplasms (mainly adenocarcinomas in endometrium, small bowel, ovarium, stomach, ureter and bladder). Clinical diagnosis is suspected because of the familial history and it is confirmed when identifying germline mutations in the DNA repair genes (mainly MLH1 and MSH2). These mutations determine a genomic instability state known as microsatellites instability, present in over 85% of tumours belonging to the Lynch syndrome and 10-15% of sporadic neoplasms. Identification of mutations and determination of microsatellites instability imply molecular technology, expensive and with limited availability. The immunohistochemical analysis of expression of mostly affected proteins (MLH1 and MSH2) can be an interesting option.