Low membranous expression of β-catenin and high mitotic count predict poor prognosis in endometrioid carcinoma of the ovary

Abstract

Mutations in the b-catenin gene are common in ovarian endometrioid carcinoma. Few studies have addressed the association of b-catenin expression with tumor characteristics and patient outcome, yielding controversial results. The purpose of this study was to retrospectively assess the expression of b-catenin in ovarian endometrioid carcinoma and correlate its expression with the Gynecologic Oncology Group's (GOG) grading system, clinicopathological characteristics, and patient survival. A total of 49 patients with primary ovarian endometrioid carcinoma were included in this study. A four-tier score grading system was used for the membranous staining (negative, weak, moderate, and strong) and the percentage of positive cells for the nuclear staining of b-catenin. The status of five morphometric parameters, nuclear morphology (uniform or pleomorphic), mitotic count, glandular pattern, degree of squamous differentiation, and status of papillary pattern, was assessed. We found that a low membranous expression of b-catenin and a high mitotic count (415 per 10 high-power fields) were significantly associated with poor prognosis and early recurrence of ovarian endometrioid carcinoma. In addition, cases with nuclear expression of b-catenin showed an intermediate overall survival risk and late disease recurrence. Young age at the time of diagnosis, advanced disease stage, and suboptimal debulking were among the clinical factors predicting poor survival and early disease recurrence. The presence of squamous differentiation, a papillary pattern or nuclear pleomorphism did not show any correlation with overall survival or disease-free survival. Low membranous expression of b-catenin and high mitotic count are poor prognostic indicators in patients with ovarian endometrioid carcinoma, whereas the GOG grading system showed no prognostic value. Our data suggest that there is a need to define a better grading system for ovarian endometrioid carcinoma. Molecular markers such as b-catenin and mitotic count could aid in defining this grading system.

Clinicopathologic study of E-cadherin/beta-catenin complex, and topoisomerase-II in a series of 71 liposarcoma cases

“…A major finding in our study was the predominately membranous localization of beta-catenin, which among STS has only been described in uterine leiomyosarcomas [21]. Since, membranous beta-catenin expression was low, if any, in our liposarcomas, definite conclusion about its association with the low metastatic potential of the majority of these tumors can not be drawn [22,23]. …”

Wnt/β-catenin pathway as a potential prognostic and predictive marker in patients with advanced ovarian cancer

“…One of the possible mechanisms of WNT/β-catenin pathway alteration involves mutations of the β-catenin gene (CTNNB1), which are found in endometrioid subtype of ovarian cancer [19-21]. Additionally, aberrant expression of β-catenin, E-cadherin and WNT-1 was observed in ovarian carcinoma [22-27]. The prognostic role of β-catenin and E-cadherin are disputed, while their impact on response to chemotherapy has never been evaluated in ovarian cancer patients.…”

Wnt Signaling and Survival of Women With High-Grade Serous Ovarian Cancer: A Brief Report

“…2 Recently, investigators also reported that patients with endometrioid OvCa with increased membrane A-catenin protein expression had decreased PFS and increased platinum resistance. 3 To further evaluate Wnt pathway genes as potential biomarkers for OvCa survival and chemotherapy response, we analyzed associations of Wnt pathway genes with survival outcomes among patients with high-grade serous OvCa treated with IP or IV chemotherapy.…”