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C Zamagni, Medical Oncology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
R Wirtz, Molecular Research Germany, Siemens Healthcare Diagnostics, Cologne, Germany
P De Iaco, Obstetrics & Gynaecology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
M Rosati, Medical Oncology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
E Veltrup, Molecular Research Germany, Siemens Healthcare Diagnostics, Cologne, Germany
F Rosati, Obstetrics & Gynaecology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
E Capizzi, Pathology Unit, University of Bologna, Bologna, Italy
N Cacciari, Medical Oncology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
C Alboni, Obstetrics & Gynaecology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
A Bernardi, Medical Oncology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
F Massari, Medical Oncology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
S Quercia, Medical Oncology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
A D'Errico Grigioni, Pathology Unit, University of Bologna, Bologna, Italy
M Dietel, Institute of Pathology, Charite Universitatsmedizin, Berlin, Germany
J Sehouli, Gynaecology and Obstetrics, Charite Universitatsmedizin, Berlin, Germany
C Denkert, Institute of Pathology, Charite Universitatsmedizin, Berlin, Germany
A Martoni, Medical Oncology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy

Correspondence: Claudio Zamagni, Email: claudio.zamagni{at}aosp.bo.it

Abstract

Oestrogen receptors regulate growth and differentiation of normal ovarian epithelia. However, up to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of oestrogen receptor 1 (ESR1) mRNA expression in ovarian cancer in the context of a neo-adjuvant chemotherapy trial. Study participants had epithelial ovarian or peritoneal carcinoma unsuitable for optimal upfront surgery and were treated with neo-adjuvant platinum-based chemotherapy before surgery. RNA was isolated from frozen tumour biopsies before treatment. RNA expression of ESR1 was determined by microarray and RT-kPCR technologies. The prognostic value of ESR1 was tested using univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival statistics and the log-rank test. ESR1 positively correlates with proliferation markers and histopathological grading. ESR1 was a significant predictor of survival as a continuous variable in univariate Cox regression analysis. In multivariate analysis elevated baseline ESR1 mRNA levels predicted prolonged progression-free survival (PFS; p=0.03) and overall survival (OAS; p=0.02) after neo-adjuvant chemotherapy, independently of pathological grade and age. We conclude that pre-treatment ESR1 mRNA is associated with tumour growth and is a strong prognostic factor in ovarian cancer, independent of the strongest clinical parameters used in clinical routine. We suggest that ESR1 mRNA status should be considered in order to minimize confounding effects in ovarian cancer clinical trials, and that early treatment with anti-hormonal agents based on reliable hormone receptor status determination is worth investigating.