Although some authors suggested to screen tumors only with antibodies against MSH6 and PMS2 proteins (two-stain method) to reduce costs [137,138] (with the subsequent staining of the partner if either is absent), it is generally recommended to test the four MMR proteins, since the two-stain immunohistochemical screening may fail to detect mismatch repair deficiency in some LS tumors [115,139]. Here, MSH6 is linked to Leigh syndrome.