Simultaneous expression of steroid sulfatase and androgen receptor reduced overall survival of patients with epithelial ovarian tumors

Argelia Calvillo-Robledo,Miguel Ángel Almaraz,Carmen Méndez,Delia Pérez-Montiel,Flavia Morales-Vásquez,Enrique Pedernera,Horacio Noé López-Basave,Paulina García De Alba Graue,María J Gómora,Elizabeth Rendón,Andrés Quintanar-Stephano

doi:10.1186/s13048-021-00840-x

Abstract

BackgroundOvarian cancer is usually diagnosed at an advanced stage due to its early asymptomatic course and late-stage non-specific symptoms. This highlights the importance of researching the molecular mechanisms involved in ovarian carcinogenesis as well as the discovery of novel prognostic markers that could help improve the survival outcome of patients. The aim of this study was to evaluate the expression of the steroid sulfatase (STS) in 154 samples of primary ovarian tumors. This protein is crucial in the intracellular conversion of sulfated steroid hormones to active steroid hormones. The presence of STS, 3β-HSD, and 17β-HSD1 result in the production of testosterone which act through the androgen receptor (AR) in the tumor cell. The presence of STS and AR in epithelial ovarian tumors and their association to the overall survival of patients was evaluated using Kaplan–Meier and Cox regression analyses.ResultsImmunoreactivity for STS was detected in 65% of the tumors and no association was observed with histological subtypes and clinical stages of the tumor. The STS expression in the tumors exhibiting immunoreactive AR resulted in a reduced survival (log-rank test, p = 0.032) and a risk factor in univariate and multivariate analysis, HR = 3.46, CI95% 1.00–11.92, p = 0.049 and HR = 5.92, CI95% 1.34–26.09, p = 0.019, respectively.ConclusionsThese findings suggest that the intracellular synthesis of testosterone acting through its receptor can promote tumor growth and progression. Moreover, the simultaneous expression of STS and AR constitutes an independent predictor of poor prognosis in epithelial ovarian tumors.

Highlights

Ovarian cancer is usually diagnosed at an advanced stage due to its early asymptomatic course and late-stage non-specific symptoms
The histological subtypes of the tumors included in the study were as follows: borderline tumors (BT) 27/154 (18%), low grade serous carcinomas 16/154 (10%), high grade serous carcinomas 44/154 (29%), endometrioid carcinoma 35/154 (23%), mucinous carcinoma 16/154 (10%), clear cells carcinoma 6/154 (4%) and 6% of another tumor subtype
The clinical features of the patients were summarized by the age at diagnosis, the reproductive status, the clinical stages of the tumor according to the FIGO scale, the histological grade registered for endometrioid carcinoma and the success of surgery (Table 1)

Summary

Introduction

Ovarian cancer is usually diagnosed at an advanced stage due to its early asymptomatic course and late-stage non-specific symptoms. This highlights the importance of researching the molecular mechanisms involved in ovarian carcinogenesis as well as the discovery of novel prognostic markers that could help improve the survival outcome of patients. The aim of this study was to evaluate the expression of the steroid sulfatase (STS) in 154 samples of primary ovarian tumors. This protein is crucial in the intracellular conversion of sulfated steroid hormones to active steroid hormones. It has been suggested that the enzymes involved in estrogen synthesis could be associated to cell proliferation in several types of cancers, such as endometrial and ovarian cancer [7, 8]

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