MP52-04 COLOCALIZATION OF ANDROGEN RECEPTOR AND ESTROGEN RECEPTOR ALPHA IN THE STROMAL MICROENVIRONMENT SUPPORTS A ROLE FOR ESTROGENS IN EARLY PROSTATE CANCER PROGRESSION

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research V1 Apr 2014MP52-04 COLOCALIZATION OF ANDROGEN RECEPTOR AND ESTROGEN RECEPTOR ALPHA IN THE STROMAL MICROENVIRONMENT SUPPORTS A ROLE FOR ESTROGENS IN EARLY PROSTATE CANCER PROGRESSION Tristan Nicholson, Priyanka Sehgal, Sally Drew, Wei Huang, and William Ricke Tristan NicholsonTristan Nicholson More articles by this author , Priyanka SehgalPriyanka Sehgal More articles by this author , Sally DrewSally Drew More articles by this author , Wei HuangWei Huang More articles by this author , and William RickeWilliam Ricke More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1614AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Androgens, acting via androgen receptor (AR), are known to be important in prostate cancer (PRCA) progression; there is also an emerging role for estrogens, acting via estrogen receptors (ERs), in PRCA. We evaluated expression and localization of AR and ERα (considered the key estrogenic mediator of prostate carcinogenesis) to better understand the role of these sex steroid receptors in PRCA progression. We asked two questions: (1) what is the prevalence of cells expressing AR, ERα and both receptors during different stages of PRCA progression, and (2) what does the relative prevalence of double positive cells imply about the underlying biology of the stromal microenvironment during PRCA progression? Methods Multiplexed immunohistochemistry was performed to detect AR, ERα and smooth muscle alpha-actin (ACTA2) utilizing a tissue microarray consisting of benign prostate tissue (BPT), high-grade prostatic intraepithelial neoplasia (HGPIN), primary tumor from PRCA, and metastasis (MET). To assess the number of sex steroid receptor positive cells and marker staining intensity, we used an automated pathology platform. Results Expression and staining intensity of AR increased with PRCA progression in prostate epithelium, carcinoma cells and the stromal microenvironment. Epithelial and stromal ERα expression and staining intensity was highest in HGPIN and decreased in PRCA and MET, relative to BPT. However, among stromal cells negative for ACTA2, AR positive cells were less prevalent in PRCA compared to BPT, and there was no significant difference in the prevalence of ERα positive cells. In the epithelium and the stromal microenvironment, double positive (for AR & ERα) cells were most prevalent in HGPIN, relative to BPT. Conclusions Taken together, the present results underscore the importance of androgens and estrogens in the biology of PRCA progression. We found an increased prevalence of cells expressing both AR and ERα in early, but not late stages of PRCA progression, suggesting that while the androgens are important in all stages of progression, the role for estrogens and sex steroid synergy may be most prominent during early prostate carcinogenesis. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e581 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Tristan Nicholson More articles by this author Priyanka Sehgal More articles by this author Sally Drew More articles by this author Wei Huang More articles by this author William Ricke More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...