HNPCC is characterized by defective MMR (80%-90% germline mutations of MLH1 and MSH2), but the majority of sporadic MSI tumors are caused only by gene silencing through hypermethylation of MLH1 promoter, and somatic inactivation of MSH2 seems to be very rare (33,34). This evidence concerns the gene MLH1 and hereditary nonpolyposis colon cancer.