β‐catenin expression in primary and metastatic colorectal carcinoma

β‐catenin plays a fundamental role in the regulation of the E‐cadherin‐catenin cell adhesion complex. It also functions in growth signalling events, independently of the cadherin‐catenin complex, and these signalling pathways are disturbed in colorectal cancer. Mutations in either the APC or β‐catenin genes in colorectal cancer cells result in up‐regulation of protein expression and subsequent cytoplasmic and nuclear distribution of β‐catenin. In this study, we examined β‐catenin expression in 47 primary colorectal tumors and the corresponding liver metastases. Immunohistochemical studies demonstrated loss of membranous β‐catenin expression in 26% of primary tumors and 60% of liver metastases and a concomitant increase in cytoplasmic and nuclear staining. Widespread nuclear expression of β‐catenin was found in 64% of primary tumors and 21% of liver metastases. No associations were found between any form of β‐catenin expression and either tumor stage or tumor grade. Cellular distribution of β‐catenin was also examined by detergent extraction and Western blot analysis in 16 primary tumors and 23 liver metastases. This analysis showed that most tumors demonstrated reduced β‐catenin in the cytoskeletal fraction and increased β‐catenin in the cytosolic fraction. Furthermore, 3 liver metastases were found to contain a truncated β‐catenin protein of approximately Mr 80,000. Immunoprecipitation studies showed that the truncated β‐catenin proteins only bound weakly to E‐cadherin and β‐catenin compared with non‐truncated β‐catenin. These results demonstrate gross alterations in the cellular distribution of β‐catenin in primary colorectal cancers with metastatic potential, as well as in the metastatic tumors. These changes may be the consequence of APC or β‐catenin gene mutations, or possibly result from a post‐translational modification of the E‐cadherin‐catenin complex. Int. J. Cancer 82:504–511, 1999. © 1999 Wiley‐Liss, Inc.