Hormone receptor expression and outcomes in low-grade serous ovarian carcinoma

Abstract

ObjectiveLow-grade serous ovarian carcinomas (LGSC) are frequently ER/PR positive, though the mechanisms by which ER/PR regulate prognosis or anti-estrogen treatment efficacy are poorly understood. We studied ER/PR expression in LGSC tumors and cell lines to evaluate patient outcomes and cellular treatment responses. MethodsLGSC tumors and patient-derived cell lines were studied from patients with advanced-stage (III/IV) disease. Tumor samples and clinical data were obtained from the Canadian Ovarian Experimental Unified Resource (COEUR-tissue microarray) and the Ovarian Cancer Research (OvCaRe) tissue bank. ER/PR expression was assessed by both Western blot and immunohistochemistry (IHC). Two different IHC scoring systems (simple and Allred) were used. Cox regression was used to identify factors (age, disease residuum, ER/PR status, etc.) associated with progression-free (PFS) and overall survival (OS). Estradiol and tamoxifen proliferation and viability experiments were performed in LGSC cell lines. ResultsIn 55 LGSC cases studied, median follow-up was 56 months (range 1–227). Fifty-three (96%) cases strongly expressed ER whereas 37 (67%) expressed PR. Cox-regression analysis showed that residuum (p < 0.001) was significantly associated with PFS, whereas both ER Allred score (p = 0.005) and residuum (p = 0.004) were significant for OS. None of the LGSC cell lines expressed PR. Loss of PR and ER expression over time was detected in LGSC tumors and cell lines respectively. Estrogen and tamoxifen treatment did not alter LGSC cell proliferation or viability in-vitro. ConclusionsIn patients with advanced LGSC, higher ER Allred scores were significantly associated with better overall survival. ER/PR expression changed over time in both LGSC tumors and cell lines. Better translational research models are needed to elucidate the molecular mechanisms of ER/PR signalling in LGSC.