11 Role of mismatch repair proteins and microsatellite instability in colon carcinoma

Publisher Summary Colorectal cancer (CRC) has long been regarded largely as an environmentally determined human cancer with dietary factors playing a major role in its initiation and/or promotion. It is only recently that genetic factors have emerged as significant in the understanding of this disease. Microsatellite instability (MSI) is the molecular fingerprint of a deficient mismatch repair system. Approximately 15% of CRC display MSI owing either to epigenetic silencing of MutL homologue 1 (MLH1) or a germline mutation in one of the mismatch repair genes MLH1, MSH2, MSH6, or PMS2. Methods to detect MSI are well established and routinely incorporated into clinical practice. MSI tumors are defined as high (H) when they show instability at two or more markers and low (L) when this occurs at only one marker. When more than five markers are adopted, tumors showing more than 30% instability at the markers used are defined as unstable. Microsatellite stable (MSS) cancer did not show instabilities at any marker.