Lack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas in hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer syndrome is associated with an in herited predisposition to primarily colorectal cancer (CRC) and endometrial cancer (EC); however, the biological basis of the organ involvement remain s unknown. As an attempt to explore whether the expression levels of MLH1, MSH2, and MSH6 may play a role, we used immunohistochemistry to study 42 EC s and 35 CRCs from patients carrying the same predisposing mutations. Among MSH2 mutation carriers, MLH1 was expressed in both tumor types, whereas MS H2 and, in many cases, also MSH6, were absent. Remarkably, among MLH1 mutat ion carriers, 54% of ECs (21 of 39), but none of the CRCs (0 of 32),lacked the MSH2 and/or MSH6 protein in addition to lacking MLH1 protein expression . These results demonstrate a marked difference between hereditary nonpolyp osis colorectal cancer-related CRCs and ECs and suggest that the developmen t of the latter tumors is selectively associated with the MSH2/MSH6 protein complex deficiency.