LEVEL OF ALPHA-CATENIN EXPRESSION IN COLORECTAL-CANCER CORRELATES WITH INVASIVENESS, METASTATIC POTENTIAL, AND SURVIVAL

Background and Objectives: Decreased expression of the E-cadherin/alph a-catenin cell-cell adhesion complex is considered to elicit detachmen t of tumor cells from primary lesions and development of metastases. T he immunohistochemical profile of alpha-catenin in colorectal cancer, as well as its correlation with differentiation, lymph node/liver meta stasis and patient survival is presented in this study. Methods: alpha -Catenin expression was investigated with immunohistochemistry techniq ue, in 85 paraffin-embedded and 21 fresh frozen specimens, including 8 2 colon adenocarcinomas, 10 adenomas, 10 lymph nodes, and 3 liver meta stases. Preserved alpha-catenin expression was considered for those tu mors that demonstrated more than 90% alpha-catenin(+) cancer cells and reduced alpha-catenin expression for those tumors with less than 90% alpha-catenin(+) cancer cells. The chi(2)-test was used to calculate t he statistical correlation of alpha-catenin expression with grade of d ifferentiation and metastatic potential and the log-rank test for the correlation with survival rate. Results: Normal mucosa, as well as 8/1 0 of the colon adenomas, showed strong membranous alpha-catenin expres sion. Reduced alpha-catenin expression was found in 32/82 (39%) colore ctal cancers examined, which was associated with de-differentiation (P < 0.01), lymph node metastasis (P < 0.025), and poor clinical outcome (P < 0.012). alpha-Catenin expression was preserved in 3 liver metast ases and their corresponding primary tumors. By contrast, 6/10 of lymp hogenous metastases showed decreased alpha-catenin expression. Conclus ions: Our findings demonstrate a significant down-regulation of alpha- catenin expression in colorectal cancer which is associated with poor differentiation, higher metastatic potential and unfavorable prognosis . These preliminary results suggest that alpha-catenin may be a useful marker of invasiveness, metastatic potential, and survival in colorec tal cancer patients. (C) 1998 Wiley-Liss, Inc.