The role of germline mutations (MLH1, MSH2, MSH6, BRAF) and deletions of EPCAM gene in familial clustering colorectal cancer and Lynch syndrome from patients of the Hospital São Paulo - Brazil

Abstract

Among the more than 1 million new cases of colorectal cancer reported worldwide each year, 2-5% are carriers of Lynch syndrome (HNPCC), less than 1% have familial adenomatous polyposis (FAP) and about 20% of familial colorectal cancer . The big challenge is to adequately detect patients with the disease so you can trigger the monitoring of the patient with the aim of detecting new tumors. Objective: To study the genetic mutations (MLH1, MSH2, MSH6, BRAF) and deletions EPCAM gene in colorectal cancer patients with familial clustering and those with clinical suspicion of Lynch syndrome. Methods: 100 patients with colorectal cancer with at least one of the Bethesda criteria will be assessed. The analysis of MSI (microsatellite instability) and the detection of the expression of DNA repair proteins (MLH1, MSH2, MSH6 and PMS2) are carried on tumor samples by immunohistochemical technique. Tumors are classified as MSI-H (high), MSI-L (low) or MSS (stable). With the MSI-H will be considered positive, while the MSI-L and MSS will be negative for the syndrome. The research of the BRAF mutation will be held at negative tumor for MLH1. The sequencing of MLH1, MSH2 will be held in MSI-H tumors without BRAF mutation. EPCAM deletions of the gene to be evaluated in exons 3, 8 and 9 with MSI tumors and low expression of MSH2. Furthermore, we analyze the expression of APC, EPCAM, ²-catenin, TCF-4, c-myc and cyclin D1 in relation to the expression of proteins EPCAM protein. (AU)