MSH6 and colorectal carcinoma: However, since MSH2 hypermethylation is reported to occur in 24% of MSH2-deficient colorectal carcinoma [29], testing for MSH2 gene promotor hypermethylation should always be performed when a loss of MSH2 and MSH6 protein expression is found by IHC, but no corresponding underlying genetic variant is detected by DNA panel sequencing.