PD47-03 EXPRESSION OF CYTOPLASMIC ERβ1 AND NUCLEAR ERβ2 IS ASSOCIATED WITH POOR OUTCOMES FOLLOWING RADICAL PROSTATECTOMY FOR LOCALIZED PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Data regarding the expression of estrogen receptors (ER) and prostate cancer (PCa) outcomes are limited. We evaluated the relationship of expression profiles of ERb; isoforms and the membrane bound estrogen receptor GPR30 with patient factors and outcomes following radical prostatectomy (RP). METHODS: Tissue microarrays constructed from 566 men who underwent RP for localized PCa were analyzed with immunohistochemistry targeting ERb1, ERb2, ERb5 and GPR30. An experienced, blinded pathologist scored receptor distributions and staining intensities. Demographic and clinical data were evaluated with descriptive statistics. Correlations between PCa ERb; isoform and GPR30 expression and clinicopathologic data were analyzed with c2 tests. Cox proportional hazards models were used to examine associations between each ER’s staining pattern and time to recurrence and prostate cancer-specific mortality (PCSM). Receptor sub-type staining patterns found to have a significant association with recurrence or PCSM were further analyzed using the Kaplan-Meier method. Significance was set at a <0.05, two-tailed test. RESULTS: PCa cells had unique staining patterns with ERb1 demonstrating predominantly nuclear localization, while ERb2, ERb5 and GPR30 were predominantly cytoplasmic. Median follow-up among was 10.5 years. After controlling for patient factors, increasing cytoplasmic ERb1 (cERb1) (HR 1.53, 95% CI 1.01-2.32, p1⁄40.047) and nuclear ERb2 (nERb2) (HR 1.55, 95% CI 1.01-2.38, p1⁄40.043) staining were associated with significantly worse 5-year recurrence-free survival (RFS). Increasing cERb1 (HR 4.67, 95% CI 1.80 e 12.11, p1⁄40.002) and nERb2 (HR 2.49, 95% CI 1.08 e 5.80, p1⁄40.033) expression were also associated with significantly increased risk of PCSM. Patients with cERb1 and nERb2 co-staining had significantly worse 15-year PCSM vs. patients expressing only cERb1, only nERb2, or neither (16.4% vs. 4.3% vs. 0.0% vs 2.0 %, respectively p1⁄40.001) (Figure). CONCLUSIONS: Increased cERb1 and nERb2 expression are associated with worse PCa-specific outcomes following RP. These findings suggest that evaluating tumor ERb1 and ERb2 staining patterns following RP may provide prognostic information Source of Funding: R01-CA056678, R01-CA092579, R03CA137799, and P50-CA097186