Morphological, molecular and genetic study of MMR-deficient colorectal cancer: Contribution of somatic tools in diagnosis of Lynch syndrome.

Abstract

e14629 Background: Lynch syndrome (LS) is the most frequent inherited colorectal cancer (CRC) syndrome, due to germline mutations in one of the mismatch repair (MMR) genes. Out of the 15% of CRCs associated with deficient DNA mismatch repair system (dMMR) that are characterized by high levels of microsatellite instability (MSI-H), only 3% are attributable to Lynch syndrome. The other 12% are sporadic, with acquired dMMR phenotype caused in tumors by hypermethylation of the promoter of gene hMLH1, often associated with BRAF V600E mutation. A probably underestimated group does not respond to any of these definitions and is called Lynch-like syndrome (LLS). The aim of the study was to compare the pathological and clinical features of the LS, LLS, and sporadic CRCs and to evaluate the contribution of somatic tools to the screening of potential LS patients. Methods: Two hundred and twelve patients with a dMMR CRC were included. The clinical, surgical, pathological and genetic data were retrieved. A complete MM...