Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival.
OBJECTIVE
Decreased expression of the E-cadherin/alpha-catenin cell-cell adhesion complex is considered to elicit detachment of tumor cells from primary lesions and development of metastases. The immunohistochemical profile of alpha-catenin in colorectal cancer, as well as its correlation with differentiation, lymph node/liver metastasis and patient survival is presented in this study.


METHODS
Alpha-Catenin expression was investigated with immunohistochemistry technique, in 85 paraffin-embedded and 21 fresh frozen specimens, including 82 colon adenocarcinomas, 10 adenomas, 10 lymph nodes, and 3 liver metastases. Preserved alpha-catenin expression was considered for those tumors 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 chi2-test was used to calculate the statistical correlation of alpha-catenin expression with grade of differentiation and metastatic potential and the log-rank test for the correlation with survival rate.


RESULTS
Normal mucosa, as well as 8/10 of the colon adenomas, showed strong membranous alpha-catenin expression. Reduced alpha-catenin expression was found in 32/82 (39%) colorectal 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 metastases and their corresponding primary tumors. By contrast, 6/10 of lymphogenous metastases showed decreased alpha-catenin expression.


CONCLUSIONS
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 colorectal cancer patients.
Raftopoulos
I
I
Second Department of Propedeutic Surgery, Laikon Hospital, Athens University Medical School, Greece.
Davaris
P
P
Karatzas
G
G
Karayannacos
P
P
Kouraklis
G
G
D000230:Adenocarcinoma / Q000737:chemistry / Q000556:secondary*; D000236:Adenoma / Q000737:chemistry / Q000473:pathology; D002448:Cell Adhesion; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D008113:Liver Neoplasms / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D016612:Paraffin Embedding; D016019:Survival Analysis; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D003598:Cytoskeletal Proteins; D051178:alpha Catenin