Some pathogenic missense variants of MMR proteins escape detection by IHC, lowering the sensitivity of the test;29,84,85,86 this was the case for two pathogenic mutations in the OSU study.2,84 It has been reported that IHC testing of MSH6 and PMS2 alone in Lynch syndrome tumours is as effective as a four-antibody test,87 and this two-antibody test is in routine use in the endometrial tumour screening programme at the Cleveland Clinic;76 however the clinical validity of the test does not appear to have been formally evaluated. This evidence concerns the gene MSH6 and Lynch syndrome.