PMS2 and colorectal carcinoma: Therefore, patients with CRC and a loss of MLH1 with the absence of the BRAF V600E mutation or MLH1 hypermethylation, as well as patients with a loss of MSH2 or MSH6 (or both) or PMS2 and elevated MSI, should be referred for genetic counseling and germline genetic testing to confirm LS [14].