Left-Sided microsatellite unstable colorectal cancers show less frequent methylation of hMLH1 and CpG island methylator phenotype than right-sided ones

CONDENSED ABSTRACT: We compared the methylation status of several loci between right-sided and left-sided colorectal cancers (CRCs). To the best of our knowledge, this is the first to report that left-sided CRCs show significantly less frequent methylation at several loci and CpG island methylator phenotype (CIMP) than right-sided ones. BACKGROUND AND OBJECTIVES: MSI CRC occurs in 10-20% of unselected series of patients with CRC. Somatic hMLH1 promoter methylation is reported to cause MSI in sporadic cases. Many researchers report that MSI CRCs are more frequently located in the right-side colon than MSS CRCs. Though the number is very small, some MSI CRCs are located in the left-side colorectum. We focused on the existence of left-sided MSI CRCs and investigated whether they arise through hMLH1 methylation as they do in right-sided ones. METHODS: Thirty-eight sporadic MSI CRCs were included in the study. The methylation status of the promoter of hMLH1, p16, MINT1, 2 and 31 were examined and the proportions of methylated samples for each locus were compared. RESULTS: The left-sided group showed significantly less frequent methylation in hMLH1, p16, MINT1, 2 and 31. The frequency of CIMP+ samples in the left-sided group was significantly lower than the right-sided group. CONCLUSIONS: Left-sided MSI CRCs show significantly less frequent methylation of hMLH1. They also showed significantly less frequent occurrence of CIMP+ than right-sided ones. It is possible that left-sided MSI CRCs differ from the right-sided ones in the way of acquiring MSI.