Tissue-specific quantification and localization of androgen and estrogen receptors in prostate cancer

Priyanka D Sehgal; Tyler M Bauman; Tristan M Nicholson; Jordan E Vellky; Emily A Ricke; Weiping Tang; Wei Xu; Wei Huang; William A Ricke

doi:10.1016/j.humpath.2019.04.009

Tissue-specific quantification and localization of androgen and estrogen receptors in prostate cancer

Hum Pathol. 2019 Jul:89:99-108. doi: 10.1016/j.humpath.2019.04.009. Epub 2019 May 3.

Authors

Priyanka D Sehgal¹, Tyler M Bauman², Tristan M Nicholson³, Jordan E Vellky⁴, Emily A Ricke⁵, Weiping Tang⁶, Wei Xu⁷, Wei Huang⁸, William A Ricke⁹

Affiliations

¹ Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
² Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; Division of Urology, Washington University School of Medicine, St Louis, MO 63110, USA.
³ Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; Department of Urology, University of Washington School of Medicine, Seattle, WA 98915, USA.
⁴ Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; Cancer Biology Graduate Program, University of Wisconsin-Madison, Wisconsin Institute for Medical Research, Madison, WI 53705, USA; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
⁵ Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; George M. O'Brien Research Center of Excellence, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
⁶ Department of Medicinal Chemistry, University of Wisconsin School of Pharmacy, Madison, WI 53705, USA.
⁷ Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; George M. O'Brien Research Center of Excellence, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA.
⁸ Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; George M. O'Brien Research Center of Excellence, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
⁹ Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; George M. O'Brien Research Center of Excellence, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA. Electronic address: rickew@urology.wisc.edu.

Abstract

Androgens and estrogens, working together, promote prostate cancer (PRCA) initiation and progression, with androgens acting via androgen receptor (AR) and estrogens acting primarily through estrogen receptor α (ERα). While the interplay between these steroid hormones has been established, the interaction between steroid hormone receptors in prostatic disease remains unstudied. The goal of this study was to objectively determine the incidence, stage specificity, and tissue/cell type specificity of AR and ERα expression, both independently and simultaneously, during the progression of PRCA. Using multiplexed immunohistochemistry and multispectral imaging analysis, AR, ERα, and smooth muscle α-actin expression was detected and quantitated in benign prostate tissue (BPT), high-grade prostatic intraepithelial neoplasia (HGPIN), PRCA, and metastasis (MET) from patient specimens (n=340). Epithelial AR expression was significantly increased in HGPIN, PRCA, and MET compared with BPT, whereas ERα expression in epithelial and stromal cells was highest in HGPIN. With analysis of AR and ERα coexpression, we identified a unique population of double-positive (AR⁺/ERα⁺) cells that increased in HGPIN specimens in both the stroma and the epithelium. Double-negative (AR^-/ERα^-) cells significantly decreased across PRCA progression, from 65% in BPT to 30% in MET. Preliminary analysis of this AR⁺/ERα⁺ population indicates potential cell type specificity in smooth muscle α-actin-negative stromal cells. This study demonstrates stage-, tissue-, and cell type-specific AR and ERα expression changes during PRCA progression, both independently and coexpressed. A more complete understanding of steroid hormones and their receptors in the initiation and progression of prostatic disease may elucidate improved strategies for PRCA prevention or therapy.

Keywords: Androgens; Epithelium; Estrogens; Prostate cancer; Stroma.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Biomarkers, Tumor / analysis*
Disease Progression
Humans
Male
Prostatic Neoplasms / metabolism*
Prostatic Neoplasms / pathology*
Receptors, Androgen / analysis
Receptors, Androgen / biosynthesis*
Receptors, Estrogen / analysis
Receptors, Estrogen / biosynthesis*

Substances

AR protein, human
Biomarkers, Tumor
Receptors, Androgen
Receptors, Estrogen

Abstract

Publication types

MeSH terms

Substances

Grants and funding