Marta Llaurado Fernandez1, Amy Dawson2, Hannah Kim3, Nicole Lam4, Holly Russell4, Maegan Bruce4, Madison Bittner4, Joshua Hoenisch5, Stephanie A Scott6, Aline Talhouk7, Derek Chiu8, Diane Provencher9, Melica Nourmoussavi10, Gabriel DiMattia11, Cheng-Han Lee12, C Blake Gilks13, Martin Köbel14, Mark S Carey15. 1. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: marta.llaurado@ubc.ca. 2. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: amy.dawson@ubc.ca. 3. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: hannah.kim@ubc.ca. 4. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. 5. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: joshua.hoenisch@alumni.ubc.ca. 6. Department of Obstetrics and Gynecology, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: stephaniea.scott@nshealth.ca. 7. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: atalhouk@bccrc.ca. 8. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: dchiu@bccrc.ca. 9. Division of Gynecologic-Oncology, Centre Hospitalier de l'Université de Montréal (CHUM) and Centre de Recherche du CHUM, Montreal, Quebec, Canada. Electronic address: diane.provencher.chum@ssss.gouv.qc.ca. 10. Division of Gynecologic-Oncology, Centre Hospitalier de l'Université de Montréal (CHUM) and Centre de Recherche du CHUM, Montreal, Quebec, Canada. 11. Department of Oncology, University of Western Ontario, London, Ontario, Canada. Electronic address: dimattia@uwo.ca. 12. Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: chenghan.lee@bccancer.bc.ca. 13. Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: blake.gilks@vch.ca. 14. Department of Pathology and Laboratory Medicine, University of Calgary, Alberta Public Lab, Calgary, Alberta, Canada. Electronic address: martin.koebel@cls.ab.ca. 15. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: mark.carey@ubc.ca.
Abstract
OBJECTIVE: Low-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. METHODS: LGSC 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. RESULTS: In 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. CONCLUSIONS: In 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.
OBJECTIVE: Low-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. METHODS:LGSC 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. RESULTS: In 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. CONCLUSIONS: In 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.
Authors: Dane Cheasley; Marta Llaurado Fernandez; Martin Köbel; Hannah Kim; Amy Dawson; Joshua Hoenisch; Madison Bittner; Derek S Chiu; Aline Talhouk; C Blake Gilks; Madawa W Jayawardana; Kathleen I Pishas; Anne-Marie Mes-Masson; Diane Provencher; Abhimanyu Nigam; Neville F Hacker; Kylie L Gorringe; Ian G Campbell; Mark S Carey Journal: NPJ Precis Oncol Date: 2022-06-29