Munday J S, Frizelle F A, Whitehead M R
Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
Vet Pathol. 2008 Jan;45(1):3-6. doi: 10.1354/vp.45-1-3.
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.
新西兰的绵羊比世界其他地方的绵羊更易患小肠腺癌。这种肿瘤高发率可能是由于遗传易感性或环境致癌物所致。区分遗传因素和环境因素很重要，因为如果存在环境致癌物，人们可能会直接接触或通过食用绵羊肉而接触到。在人类中，错配修复（MMR）基因的种系缺陷会导致遗传性非息肉病性结直肠癌（HNPCC）。患病个体易患肿瘤，最常见的是结肠腺癌。据推测，MMR缺陷在新西兰绵羊群体中很常见，这些缺陷使新西兰绵羊易患肠道肿瘤。为了对此进行研究，采用免疫组化方法评估了49例绵羊小肠腺癌中MMR蛋白MSH2、MSH6、MLH1和PMS2的表达情况。所有绵羊肿瘤中的肿瘤细胞均表达MSH2、MSH6和MLH1。无法评估PMS2的表达，很可能是因为抗人PMS2抗体对绵羊PMS2的亲和力不足。绵羊小肠腺癌中MSH2、MSH6和MLH1的一致表达并不支持MMR基因缺陷在新西兰绵羊中很常见这一假设。
