The MMR proteins function as heterodimeric complexes: MLH1 with PMS2 (or PMS1) and MSH2 with MSH6 (or MSH3).28 As some of these proteins are unstable when not paired in a complex, a defective MMR system may involve loss of expression of more than one protein: tumours of individuals with germline MLH1 mutations generally lack both MLH1 and PMS2 expression, while those with a germline MSH2 mutation (or, more rarely, a deletion in the EPCAM gene) lack both MSH2 and MSH6 expression. This evidence concerns the gene MSH6 and neoplasm.