Dysregulation of beta-vatenin is common in canine sporadic colorectal tumors

Human colorectal tumorigenesis is often initiated by APC (adenomatous polyp osis coli) or beta-catenin (CTNNB1) mutations, which result in dysregulatio n of beta-catenin expression, followed by alterations in E-cadherin and/or p53. We examined 32 canine intestinal tumors for expression and intracellul ar distribution of beta-catenin, E-cadherin, and p53 using immunohistochemi stry. beta-Catenin in normal mucosal epithelial cells was restricted to lat eral cell membranes, but 13/13 (100%) colorectal adenomas had intense cytop lasmic and/or nuclear reactivity. Three of six (50%) colorectal carcinomas, 2/13 (15%) small intestinal carcinomas, and dysplastic cells in 1/2 focal hyperplastic lesions in the small intestine had a similar pattern of staini ng; remaining tumors had normal membranous beta-catenin reactivity. There w as a correlation (P = 0.007) between abnormal beta-catenin and E-cadherin s taining with 11/13 (85%) colorectal adenomas, 3/6 (50%) colorectal carcinom as, and 3/13 (23%) small intestinal carcinomas showing decreased membranous reactivity compared with normal mucosal epithelium. E-cadherin staining wa s reduced more often in adenomas than in carcinomas (P = 0.04). There were two patterns of nuclear p53 staining: >60% of nuclei in 2/26 (8%) carcinoma s tone colorectal, one small intestinal) were strongly labeled, whereas thr ee colorectal adenomas and one small intestinal carcinoma had fainter stain ing in 10-20% of cells. Dysregulation of beta-catenin appears to be as impo rtant in canine colorectal tumorigenesis as it is in the human disease and could be due to analogous mutations. Malignant progression in canine intest inal tumors does not appear to be dependent on loss of E-cadherin or beta-c atenin expression or strongly associated with overexpression of nuclear CM1 antibody-reactive p53.