Abstract 1834: Sex hormone receptor expression affects ovarian cancer survival
Authors: Jönsson Jenny-Maria , Arildsen Nicolai , Malander Susanne , Måsbäck Anna , Werner Hartman Linda , Nilbert Mef , Hedenfalk Ingrid 
Published: August 2015

Abstract
Background and aims: Influence of sex hormones in ovarian cancer is of great interest, but study results are inconclusive. A majority of all ovarian cancers display high expression of sex hormone receptors, but the effect of endocrine treatment is limited. We assessed estrogen (ER) α and β, progesterone (PR), and androgen (AR) receptor expression in an ovarian cancer cohort in order to study the potential correlation between receptor expression and disease free survival. Expression of the genes encoding the respective receptors (ESR1, ESR2, PGR and AR), was further explored in molecular ovarian cancer subtypes.
Methods: 140 ovarian cancers were collected in Sweden 1998-2000. A majority of the tumors were serous, high-grade and advanced stage. Immunohistochemical stainings for the receptors were evaluated on a tissue microarray, and dichotomized as either negative (&lt;10%) or positive (&gt;10% stained cells). The 5-year disease free survival (DFS) was estimated and Cox regression was used for multivariable modelling. ESR1, ESR2, PGR and AR were analyzed using an independent dataset (n = 285 tumors). Progression free (PFS) and overall survival (OS) for high versus low gene expression was analyzed in the six molecular ovarian cancer subtypes, using the median as cut-off.
Results: Immunohistochemical expression of PR and AR were both associated with increased 5-year DFS (p&lt;0.001, Log Rank test), whereas no such association was observed for ERα or ERβ. The independent effect of PR and AR was retained in multivariable analyses adjusted for stage and age. An additional effect on survival in cases expressing both PR and AR was seen, though the evidence of such an interaction was very weak (p = 0.10, Cox regression).
Gene expression analyses revealed higher mRNA levels of PGR in the molecular subtypes constituted of borderline and endometrioid tumors respectively (p&lt;0.001, Kruskal Wallis test). In the molecular subtypes, improved PFS was seen in cases with dual high expression of PGR and AR in the immunoreactive subtype, although this effect could not be proven (p = 0.23). However, tumors which expressed high levels of PGR and were of this subtype showed an improved OS (p = 0.041). In contrast, improved OS for PGR low and ESR1 high tumors was seen in the mesenchymal subtype, although the evidence was weak (p = 0.091 and p = 0.064 respectively, Log Rank test).
Conclusions: This study indicates that PR and AR may serve as independent prognostic markers in subsets of ovarian cancer, with the best 5-year disease free survival seen with combined PR/AR positivity. Gene expression analysis of the corresponding genes revealed differences among the subtypes of ovarian cancer. This underlines the importance of stratifying tumors also based on molecular features when investigating prognostic markers. Larger, well defined study cohorts are needed to identify the best markers and to elucidate in which specific subtypes of ovarian cancer endocrine treatment may have a role.
Citation Format: Jenny-Maria Jönsson, Nicolai Arildsen, Susanne Malander, Anna Måsbäck, Linda Werner Hartman, Mef Nilbert, Ingrid Hedenfalk. Sex hormone receptor expression affects ovarian cancer survival. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1834. doi:10.1158/1538-7445.AM2015-1834