Dysregulated expression of β-catenin marks early neoplastic change in Apc mutant mice, but not all lesions arising in Msh2 deficient mice

We have analysed the pattern of beta-catenin expression by immunohistochemistry in mice singly or multiply mutant for Ape, p53 and Msh2. We observed increased expression of beta-catenin in all intestinal lesions arising on an Apc(Min) +/- background. In all categories of lesion studied mosaic patterns of beta-catenin expression were observed, with the proportion of cells showing enhanced expression decreasing with increasing lesion size. p53 statics did not alter these patterns. We also show that beta-catenin dysregulation marks pancreatic abnormalities occurring in Apc(Min) +/- and (Apc(Min) +/-, p53-/-) mice. In these mice both adenomas and adenocarcinomas of the pancreas arose and were characterized by increased expression of beta-catenin, We have extended these analyses to intestinal lesions arising in mice mutant for the mismatch repair gene Msh2, In these mice, increased expression of beta-catenin was again observed. However, in contrast with Apc(Min) +/- mice, a subset of lesions retained normal expression. Taken together, these findings show that increased expression of beta-catenin is an efficient marker of early neoplastic change in both murine intestine and pancreas in Ape mutant mice. However, we also show that dysregulation of beta-catenin is not an obligate step in the development of intestinal lesions, and therefore that genetic events other than the loss of Ape function may initiate the transition from normal to neoplastic epithelium.