Reciprocity between membranous and nuclear expression of beta-catenin in colorectal tumours

beta-Catenin has a central role not only in linking the cadherin-mediated cell adhesion system but also in the intercellular signalling pathway. To investigate alterations of beta-catenin in the development of colorectal carcinoma, the pattern of beta-catenin expression was studied using immunohistochemistry in 74 sporadic colorectal adenomas, in histologically normal mucosa adjacent to 65 of these adenomas, and in 52 carcinomas arising in adenomas. All normal epithelia displayed cell boundary staining for beta-catenin. Adenomas and carcinomas showed varying degrees of membranous staining. However, some tumours also showed nuclear staining of beta-catenin protein. Decreased membranous and increased nuclear beta-catenin staining were associated with increasing degrees of dysplasia in adenomas (P < 0.005, P < 0.05, respectively). Carcinomas manifested significantly reduced membranous, but enhanced nuclear beta-catenin expression compared with their associated adenomas (P < 0.001, P < 0.005, respectively). An inverse correlation was found between decreased membranous and increased nuclear staining of beta-catenin in both adenomas and carcinomas (P < 0.025, P < 0.05, respectively). The data confirm that reduced membranous and increased nuclear expression of beta-catenin is associated with the progression of colorectal adenomas to carcinomas. Our results also suggest that decreased membranous expression of beta-catenin may result from aberrant localisation of the protein in the cell nucleus.