title: Loss of beta-catenin is associated with poor survival in ovarian carcinomas.
abstract: 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.
authors.affiliation: Instituto Português de Oncologia Francisco Gentil, Centro Regional do Norte, Departamento e Anatomia Patológica, Porto, Portugal. cristinafaleiro@mail.com
authors.forename: Cristina
authors.initials: C
authors.lastname: Faleiro-Rodrigues
authors.forename: Isabel
authors.initials: I
authors.lastname: Macedo-Pinto
authors.forename: Deolinda
authors.initials: D
authors.lastname: Pereira
authors.forename: Carlos Silva
authors.initials: CS
authors.lastname: Lopes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051180:Desmoplakins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality*; D011379:Prognosis; D016019:Survival Analysis; D015534:Trans-Activators / Q000378:metabolism*; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: D014408:Biomarkers, Tumor; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin