Both MGMT promoter hypermethylation and negative MGMT expression were noted only in cases of mucinous or clear cell carcinoma in which MSI status were mostly MSS-phenotyped; however, no significant correlation was found between MSI status and clinicopathological parameters.
The MSI-H phenotype was related to methylation of MLH1 as expected, while the MSS phenotype was related to methylation of p16(INK4a) and O(6)-methylguanine-DNA methyltransferase, although this was not statistically significant.
Among the CIMP-low group, tumours with both MGMT methylation and loss were far more frequent in MSI-low tumours (67%, 12/18) than MSI-high tumours (5.6%, 1/18; p = 0.0003) and microsatellite stable (MSS) tumours (33%, 52/160; p = 0.008).
Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival.
K-RAS mutation, loss of heterozygosity, and MLH1 and MGMT hypermethylation analyses were performed, as well as clinical features being scrutinized, to examine possible differences between MSI-L and MSS tumors using all of the possible cutoff levels for MSI-L.