Overexpression of the human hyperplastic discs protein EDD is an independent predictor of relapse in serous epithelial ovarian cancer

Abstract

5057 Background: EDD is the human orthologue of the Drosophila hyperplastic discs tumor suppressor gene that encodes a HECT domain E3 ubiquitin protein ligase and may have a role in DNA repair as well as protein degradation. It is amplified and over-expressed in a variety of cancers including serous epithelial ovarian cancer (SOC) (Clancy JL et al. Oncogene 22: 5070, 2003). In this study we sought to determine the prognostic potential of EDD protein (EDDp) expression in SOC. Methods: Using immunohistochemistry on tissue microarrays, we examined EDDp expression in 154 cases of SOC treated with surgical debulking and adjuvant chemotherapy. Expression was correlated with clinicopathological parameters and patient outcome. Results: Median follow-up time was 28 months; median survival was 28 months. Increased EDDp expression correlated with preoperative CA125 level (p=0.025) and relapse (p=0.02) but not FIGO stage, grade, age, residual disease, PS or menopausal status. Univariate predictors of relapse-free survival were stage, volume of residual disease >2cm and EDDp, all of which remained significant in multivariate analysis. Univariate predictors of overall survival were stage, grade, PS and residual disease but not EDDp (p=0.17) while in multivariate analysis grade became non-significant (p=0.06). The effect of EDDp on outcome did not vary based on the type of adjuvant chemotherapy received (platinum, taxane or alkylating agents). Conclusions: EDDp over-expression independently predicted time to relapse but not overall survival in SOC. This observation deserves further evaluation with longer follow-up in our cohort and others. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis