RECIPROCITY BETWEEN MEMBRANOUS AND NUCLEAR EXPRESSION OF BETA-CATENININ COLORECTAL TUMORS

beta-Catenin has a central role not only in linking the cadherin-media ted cell adhesion system but also in the intercellular signalling path way. To investigate alterations of beta-catenin in the development of colorectal carcinoma, the pattern of beta-catenin expression was studi ed using immunohistochemistry in 74 sporadic colorectal adenomas, in h istologically normal mucosa adjacent to 65 of these adenomas, and in 5 2 carcinomas arising in adenomas. All normal epithelia displayed cell boundary staining for beta-catenin. Adenomas and carcinomas showed var ying degrees of membranous staining. However, some tumours also showed nuclear staining of beta-catenin protein. Decreased membranous and in creased 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 n uclear beta-catenin expression compared with their associated adenomas (P < 0.001, P < 0.005, respectively). An inverse correlation was foun d between decreased membranous and increased nuclear staining of beta- catenin in both adenomas and carcinomas (P < 0.025, P < 0.05, respecti vely). The data confirm that reduced membranous and increased nuclear expression of beta-catenin is associated with the progression of color ectal adenomas to carcinomas. Our results also suggest that decreased membranous expression of beta-catenin may result from aberrant localis ation of the protein in the cell nucleus.