Mismatch repair protein expression in ovine intestinal adenocarcinomas

Sheep in New Zealand develop small intestinal adenocarcinomas more frequently than sheep elsewhere in the world. This high rate of neoplasm development could be due to a genetic predisposition or due to an environmental carcinogen. Differentiation between a genetic and an environmental factor is important as, if an environmental carcinogen is present, people could be exposed directly or by consuming sheep meat. In humans, germline defects in the mismatch repair (MMR) genes cause hereditary nonpolyposis colorectal cancer (HNPCC). Affected people are predisposed to neoplasm development, most commonly colonic adenocarcinomas. It was hypothesized that MMR defects are common within the New Zealand sheep flock, and these defects predispose New Zealand sheep to intestinal neoplasia. To investigate this, immunohistochemistry was used to evaluate the expression of the MMR proteins MSH2, MSH6, MLH1, and PMS2 within 49 ovine intestinal adenocarcinomas. Neoplastic cells within all sheep tumors expressed MSH2, MSH6, and MLH1. Expression of PMS2 could not be assessed, most likely because of insufficient affinity of the anti-human PMS2 antibody to ovine PMS2. The consistent expression of MSH2, MSH6, and MLH1 within the ovine intestinal adenocarcinomas does not support the hypothesis that defects in the MMR genes are common in New Zealand sheep.