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

• Published in: International journal of cancer Vol. 95; no. 3; pp. 194 - 197
• Main Authors: Qiao, Qilu, Ramadani, Marco, Gansauge, Susanne, Gansauge, Frank, Leder, Gerd, Beger, Hans G.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 20.05.2001; Wiley-Liss
• Subjects: Adult; Aged; Aged, 80 and over; b-catenin; beta Catenin; Biological and medical sciences; Biomarkers, Tumor - metabolism; Blotting, Western; Cell Membrane - metabolism; cyclin D1; Cyclin D1 - metabolism; Cytoplasm - metabolism; Cytoskeletal Proteins - metabolism; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; pancreatic cancer; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - mortality; Precipitin Tests; Prognosis; survival; Survival Analysis; Trans-Activators; Tumors; β‐catenin; Adenocarcinoma; Human; Membrane protein; Prognosis; Beta-Peptide chain; Cell adhesion molecule; Gene overexpression; Malignant tumor; Ectopic secretion; Cyclin D1; C-Onc gene; Digestive diseases; Genetics; Pancreas; Catenin; Cytoplasm; Protooncogene; Pancreatic disease
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/1097-0215(20010520)95:3<194::AID-IJC1033>3.0.CO;2-M

β‐Catenin is a component of the E‐cadherin–catenin cell adhesion complex. It plays also a role in intracellular signaling and can function as an oncogene when it binds to the T‐cell factor 4 (Tcf4)‐binding site in the promoter region of cyclin D1 and transactivates genes after translocation to the nucleus. We evaluated the immunohistochemical expression pattern of β‐catenin in relationship with cyclin D1 overexpression, tumor grade, clinicopathologic 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 β‐catenin expression (25 of 43, 58.1%) and accumulation of β‐catenin in the cytoplasm (28 of 43, 65.1%) correlated significantly with cyclin D1 overexpression (both p < 0.0005). Furthermore, we could show a clear correlation between reduced membranous expression and ectopic cytoplasmic expression of β‐catenin (p < 0.0005). Among patients with carcinomas showing no cytoplasmic expression, the 1‐year survival was 86.6% whereas among patients with carcinomas showing cytoplasmic expression only 35.7% survived 1 year (p < 0.01). Co‐precipitation experiments revealed reduced β‐catenin bound to the E‐cadherin–catenin complex in pancreatic tumor tissues compared with normal pancreatic tissues. These results suggest that β‐catenin may be involved in the tumorigenesis of pancreatic cancer and exhibited its effects mainly by the transactivation of cyclin D1. © 2001 Wiley‐Liss, Inc.