MLH1 and colorectal carcinoma: Furthermore, some pathogenic variants in MSH6 have been shown to associate with tumor MSS.38 The identification of MLH1 protein loss enables methylation analysis, which can exclude women with somatic MLH1 loss from unnecessary NGS.38 Methylation-specific polymerase chain reaction (PCR) is simple and cost-effective, however validation work has been almost exclusively in the CRC population.39,40 Methylation-specific PCR is not widely available, with only specialist laboratories offering this test.