Loss of beta-catenin is associated with poor survival in ovarian carcinomas.

The catenins (alpha-, beta- and gamma-) are cytoplasmic proteins that bind to the conserved tail of the epithelial cadherin molecule. The function of epithelial cadherin at the adherens junctions is dependent on the catenins for efficient cell-to-cell adhesion. Loss of catenin expression has been reported in several human cancers and associated with poor tumor differentiation, advanced tumor stage, and poor patient survival. In this study, we investigated the clinical relevance of alpha-, beta-, and gamma-catenin immunoexpression in 104 cases of primary ovarian carcinoma with respect to clinicopathological features and as predictors of disease recurrence and prognosis. The clinicopathological parameters studied were International Federation of Gynaecology and Obstetrics (FIGO) stage, histological type, tumor differentiation, peritoneal metastases, residual postoperative tumor, integrity of the tumor's serosal surface, peritoneal cytology, and lymphatic/vascular invasion. Negative immunoreactivity of alpha-catenin, beta-catenin, and gamma-catenin was observed in 22 (21%), 15 (14%) and 23 (22%) cases, respectively. Immunoreactivity of alpha-catenin and gamma-catenin did not correlate with any of the clinicopathological parameters tested. The immunoexpression pattern of beta-catenin correlated with histological type (p = 0.026) and with a poorer overall survival in univariate analyses (p = 0.022). In the group of serous carcinomas, beta-catenin-immunoexpression associated significantly with overall survival. Patients with beta-catenin-negative serous carcinomas had a poorer overall survival than patients with beta-catenin-positive serous carcinomas (p = 0.013). In the multivariate analysis, negative expression of beta-catenin (p = 0.003) and the presence of residual tumor (p = 0.019) were the two most important independent prognostic factors predicting poorer overall survival. In conclusion, negative immunoreactivity of beta-catenin in serous carcinomas and the presence of residual tumor seem to be useful markers in selecting patients likely to have an unfavorable course.

Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas.

Epithelial cadherin forms a complex with alpha-, beta-, and gamma-catenin proteins. Reduced expression of E-cadherin-catenins has been shown in human carcinomas and is associated with low histologic differentiation, increased risk of invasion, and metastatic disease. The immunoexpression pattern of E-cadherin and beta-catenin (reduced versus preserved phenotype) was evaluated in 104 primary ovarian carcinomas and related to clinicopathologic features of the tumors. The immunoexpression pattern of E-cadherin was associated with International Federation of Gynaecology and Obstetrics (FIGO) staging (P = 0.043), histologic subtype (P = 0.001), peritoneal metastasis (P = 0.006), and residual tumor (P = 0.036). The reduced phenotype of E-cadherin that was observed in 64% of the carcinomas (67/104) was associated with advanced stage tumors, serous carcinomas, presence of peritoneal metastasis, and residual tumor larger than 2 cm. The immunoexpression pattern of beta-catenin was associated with histologic subtype (P = 0.005), tumor differentiation (P = 0.025), and peritoneal metastasis (P = 0.041). The reduced phenotype of beta-catenin that was observed in 74% of the carcinomas (77/104) was associated with advanced stage tumors, poorly differentiated serous and clear cell carcinomas, presence of peritoneal metastasis, and residual tumor. The immunoexpression pattern of E-cadherin was correlated with beta-catenin (P = 0.001). The reduced phenotype for both E-cadherin and beta-catenin was associated with histologic subtype (P < 0.001) and peritoneal metastasis (P = 0.001). In conclusion, the immunohistochemical profile of E-cadherin and beta-catenin may be useful in identifying a particular subpopulation of ovarian cancer patients who are characterized by an adverse clinical outcome, because the reduced phenotype of these molecules was associated with poor tumor differentiation, peritoneal metastasis, and advanced FIGO stage tumors.