ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2014) 35 P650 | DOI: 10.1530/endoabs.35.P650

Relevance of estrogen activating STS and inactivating SULT1E1 enzymes and estrogen receptors [alpha/beta] in patients with advanced ovarian cancer

Felicitas Mungenast1, Stefanie Aust2, Martin Svoboda1, Katharina Ocko1, Lukas Klameth1, Dan Cacsire Castilo-Tong2, Robert Zeillinger2, Toon Van Gorp3, Ignace Vergote4, Ioana Braicu4, Jalid Sehouli5, Sven Mahner6, M Fogel7 & Theresia Thalhammer1

1Department of Pathophysiology and Allergy Research, Vienna, Austria; 2Molecular Oncology Group, Clinic for Gynecology and Obstectics, Medical University of Vienna, Vienna, Austria; 3Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Universitaire Leuven, Leuven, Belgium; 4Ziekenhuizen Leuven, KatholiekeUniversiteit Leuven, Leuven, Belgium; 5Department of Gynecology and Gynecologic Oncology, Berlin, Germany; 6University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 7Department of Pathology, Kaplan Medical Centre, Rehovot, Israel.

Background: By regulating the concentration of active estrogens in tumor cells, steroid hormone-inactivating estrogen sulfotransferase (SULT1E1) and estrogen activating steroid sulfatase (STS) may influence the progression of EOC. Therefore, we determined the expression and prognostic impact of both enzymes together with the ERα/β and the progesterone receptor (PGR) in this tumor entity.

Methods: The mRNA expression levels of STS, SULT1E1, ERα/β, and PGR were assessed by quantitative RT-PCR and in a large and well-described advanced stage EOC patient cohort (n=194). Protein abundance was determined by immunohistochemistry using an automated quantitative microscopic image analysis system (TissueFAXS, TissueQuest). mRNA and protein levels were correlated with each other and with clinicopathological parameters. Finally, the prognostic values of these inactivating or activating enzymes and the hormone receptors were determined.

Results: Multiple Cox regression analysis showed a significant independent impact of ERα mRNA expression on overall survival (HR=0.87; 95% CI 0.78–0.96), while STS, SULT1E1 as well as ERβ did not have an independent impact on overall- or progression free survival. Remarkably, STS mRNA levels were significantly higher in EOCs from premenopausal women (P=0.008). Immunohistochemical analysis showed that ERα was associated with STS (P=0.002) and SULT1E1 (P=0.030) levels in EOC tumor tissue. A significant correlation was also observed between high STS and high SULT1E1 abundance (P=0.021). However, no association was seen between STS, SULT1E1 and PGR. In contrast to ERα, ERß was mainly undetectable in EOC tissue.

Summary and conclusion: In patients with advanced stage EOC, the high levels of ERα, STS and SULT1E1 indicate the importance of estrogen signalling in this tumor entity. This warrants further investigations on the role of the estrogen homeostasis as a target for therapeutic intervention in EOC.