Abstract 4768: Frequency and prognostic value of hormone receptor expression in epithelial ovarian cancer.
Authors: van Kruchten Michel , van der Marel Pauline W. , Arts Henriëtte J.G. , Hollema Harry , de Munck Linda , van der Sluis Tineke , Timmer-Bosscha Hetty , Hospers Geke A.P. , Reyners An K.L. 
Published: August 2014

Introduction: Ovarian cancer (OC) is the second most common and most lethal gynecological cancer. High recurrence rate and poor prognosis underline the need to explore targeted therapies. Potential targets include hormone receptors (androgen receptor [AR], estrogen receptor α [ERα], estrogen receptor β [ERβ], and progesterone receptor [PR]). Clinical studies have shown modest effects of endocrine agents in phase II studies. Nevertheless, the role of hormones and their putative receptors in OC remains largely unknown. To further probe their role, tumor material for hormone receptor analysis was obtained from a group of patients who were treated in a prospective clinical trial. Methods: Between March 2003 and November 2008, 196 epithelial OC patients were included in a prospective multicenter randomized controlled phase II trial and assigned to carboplatin/docetaxel ± celecoxib. The majority (92.5%) of patients had high-stage disease. Histologic material for biomarker analysis was obtained from 121 patients. Histological subtypes were serous (70%), endometrioid (17%), clearcell (9%), and mucinous (4%). Mean PFS and OS were 16 and 32 months. Tissue micro arrays (4 cores/sample) were constructed and stained for AR, ERα, ERβ, and PR and scored semi-quantitatively by two independent observers. A cut-off of &gt;10% positive staining was used to dichotomize results. Receptor expression was correlated to PFS and OS in uni- and multivariate analysis (including age, FIGO stage, grade, histological subtype, and residual disease after surgery). Results: Tumors were positive for AR, ERα, ERβ, and PR in 10%, 31%, 78%, and 21% of the cases. ERα-positivity was significantly correlated with ERβ-positivity (p = 0.021). Both ERα- and ERβ-positivity were significantly correlated with AR-positivity (p &lt;0.001; p = 0.041). From 67 patients, also tissue of synchronous omental metastases was available. Gain of receptor expression was observed in 9-23% of the omental metastases compared to the primary tumor. Loss of receptor expression was observed in 9-19%. In multivariate analysis, ERβ staining of the primary tumor was associated with decreased PFS and OS (HR 1.85, p = 0.073; HR 2.15, p = 0.048). Conclusion: We showed that steroid receptors are present in a significant subpopulation of OC tumors and have prognostic value. Based on literature they can serve as potential targets for adjuvant and palliative endocrine therapy. Effects of endocrine therapy can probably be improved by taking into account heterogeneity of receptor expression. Evaluation of the predictive value of hormone receptor expression for response to endocrine therapy in OC therefore deserves further evaluation.

Citation Format: Michel van Kruchten, Pauline W. van der Marel, Henriëtte J.G. Arts, Harry Hollema, Linda de Munck, Tineke van der Sluis, Hetty Timmer-Bosscha, Geke A.P. Hospers, An K.L. Reyners. Frequency and prognostic value of hormone receptor expression in epithelial ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4768. doi:10.1158/1538-7445.AM2013-4768