MLH1 and Lynch syndrome: Impairment of MMR genes can occur in two different ways: sporadic MSI due to an epigenetic mechanism with promoter hypermethylation of the mismatch repair gene MLH1 resulting in the silencing of this gene [6], and the familial form of MSI (Lynch syndrome) in patients bearing germline mutations in the mismatch repair genes MLH1, PMS2, MSH6 or MSH2, which accounts for about 80% of MSI CRCs [59,60].