Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival

Abstract

Background and Aims: Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival in epithelial ovarian cancer. Methods: Immunohistochemical stainings for ERα, ERβ, PR, and AR were assessed in relation to survival in 118 serous and endometrioid ovarian cancers. Expression of the genes encoding the four receptors was studied in relation to prognosis in the molecular subtypes of ovarian cancer in an independent data set, hypothesizing that the expression levels and prognostic impact may differ between the subtypes. Results: Expression of PR or AR protein was associated with improved 5-year progression-free (P = .001 for both) and overall survival (P < .001 for both, log-rank test). ERα and ERβ did not provide prognostic information. Patients whose tumors coexpressed PR and AR had the most favorable prognosis, and this effect was retained in multivariable analyses. Analyses of the corresponding genes using an independent data set revealed differences among the molecular subtypes, but no clear relationship between high coexpression of PGR and AR and prognosis. Conclusions: A favorable outcome was seen for patients whose tumors coexpressed PR and AR. Gene expression data suggested variable effects in the different molecular subtypes. These findings demonstrate a prognostic role for PR and AR in ovarian cancer and support that tumors should be stratified based on molecular as well as histological subtypes in future studies investigating the role of endocrine treatment in ovarian cancer.

The role of the androgen receptor in ovarian cancer carcinogenesis and its clinical implications

“…Conversely, Nodin et al [64] reported that AR positivity predicted a prolonged disease-specific survival in the serous subtype of epithelial ovarian cancer. This data is supported by two recent studies: one using the TCGA RNA-sequencing data, demonstrated that low AR expression was associated with shorter overall survival [65] in high-grade serous ovarian carcinoma while the other using immunohistochemical staining in 118 serous and endometrioid ovarian cancers reported that high level of AR was correlated with improved 5-year progression-free and overall survival [24]. Collectively, these results support the notion that increased AR expression tends to predict a favorable prognosis in epithelial ovarian cancer, especially in serous carcinoma of the ovary.…”

“…A study by Jonsson et al [24] demonstrated that AR negativity was associated with high grade carcinomas. In contrast, four previous studies reported that no association was observed between AR scores and tumor FIGO stages in malignant ovarian tumors [21, 23, 25, 27].…”

Prognostic Significance of Hormonal Receptor Status of Malignant Ovarian Tumors

“…On the other hand, results of our study contradict the data of the other studies which have determined that high expression of androgen receptors is a favorable prognostic factor in patients with serous OC [30,44].…”

“…Certain studies have determined high survival of OC patients at expression of ER and PR in tumor [21][22][23]. Other studies showed that expression of PR and receptor to testosterone (TR) are favorable prognostic factors, and expression of ER is associated with progression of disease and short relapse-free period [24][25][26][27][28][29][30][31].…”

Clinico‑morphological aspects and new immunohistochemistry characteristics of ovarian high‑grade serous carcinoma

“…We observed that AR<10% is characteristic of 90% of tumors. Previous studies have shown that AR negativity is associated with high-grade tumors, together with the decrease of expression associated with recurrent disease and poor prognosis [23][24][25] . The androgen receptor also decreases after chemotherapy 26 .…”