Reduced membranous and ectopic cytoplasmic expression of beta-catenin correlate with cyclin D1 overexpression and poor prognosis in pancreatic cancer

beta -Catenin is a component of the E-cadherin-catenin cell adhesion comple x. It plays also a role in intracellular signaling and can function as an o ncogene when it binds to the T-cell factor 4 (Tcf4)-binding site in the pro moter region of cyclin D1 and transactivates genes after translocation to t he nucleus. We evaluated the immunohistochemical expression pattern of beta -catenin in relationship with cyclin D1 overexpression, tumor grade, clini copathologic parameters and patients' survival in 43 ductal adenocarcinomas of the pancreas and 5 normal pancreatic tissues. We were able to show that , both reduced membranous beta -catenin expression (25 of 43, 58.1%) and ac cumulation of beta -catenin in the cytoplasm (28 of 43, 65.1%) correlated s ignificantly with cyclin DI overexpression (both p < 0.0005), Furthermore, we could show a clear correlation between reduced membranous expression and ectopic cytoplasmic expression of <beta>-catenin (p < 0.0005), Among patie nts with carcinomas showing no cytoplasmic expression, the 1-year survival was 86.6% whereas among patients with carcinomas showing cytoplasmic expres sion only 35.7% survived 1 year (p < 0.01), Co-precipitation experiments re vealed reduced beta -catenin bound to the E-cadherin-catenin complex in pan creatic tumor tissues compared with normal pancreatic tissues. These result s suggest that beta -catenin mar be involved in the tumorigenesis of pancre atic cancer and exhibited its effects mainly by the transactivation of cycl in D1, (C) 2001 Wiley-Liss, Inc.