Prostate Cancer Expression Profiles of Cytoplasmic ERβ1 and Nuclear ERβ2 are Associated with Poor Outcomes following Radical Prostatectomy

J Urol. 2016 Jun;195(6):1760-6. doi: 10.1016/j.juro.2015.12.101. Epub 2016 Jan 22.

Abstract

Purpose: Existing data regarding the expression of estrogen receptors (ERs) and prostate cancer outcomes have been limited. We evaluated the relationship of expression profiles of ERβ subtypes and the ER GPR30 (G-protein-coupled receptor-30) with patient factors at diagnosis and outcomes following radical prostatectomy.

Materials and methods: Tissue microarrays constructed using samples from 566 men with long-term clinical followup were analyzed by immunohistochemistry targeting ERβ1, ERβ2, ERβ5 and GPR30. An experienced pathologist scored receptor distribution and staining intensity. Tumor staining characteristics were evaluated for associations with patient characteristics, recurrence-free survival and prostate cancer specific mortality following radical prostatectomy.

Results: Prostate cancer cells had unique receptor subtype staining patterns. ERβ1 demonstrated predominantly nuclear localization while ERβ2, ERβ5 and GPR30 were predominantly cytoplasmic. After controlling for patient factors intense cytoplasmic ERβ1 staining was independently associated with time to recurrence (HR 1.7, 95% CI 1.1-2.6, p = 0.01) and prostate cancer specific mortality (HR 6.6, 95% CI 1.8-24.9, p = 0.01). Intense nuclear ERβ2 staining was similarly independently associated with prostate cancer specific mortality (HR 3.9, 95% CI 1.1-13.4, p = 0.03). Patients with cytoplasmic ERβ1 and nuclear ERβ2 co-staining had significantly worse 15-year prostate cancer specific mortality than patients with expression of only cytoplasmic ERβ1, only nuclear ERβ2 and neither ER (16.4%, 4.3%, 0.0% and 2.0 %, respectively, p = 0.001).

Conclusions: Increased cytoplasmic ERβ1 and nuclear ERβ2 expression is associated with worse cancer specific outcomes following radical prostatectomy. These findings suggest that tumor ERβ1 and ERβ2 staining patterns provide prognostic information on patients treated with radical prostatectomy.

Keywords: prognosis; prostatectomy; prostatic neoplasms; receptors, estrogen; tissue array analysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Estrogen Receptor beta / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism
  • Prognosis
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostate / surgery
  • Prostatectomy / adverse effects
  • Prostatectomy / methods*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / surgery
  • Receptors, Estrogen / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*
  • Retrospective Studies
  • Survival Analysis
  • Tissue Array Analysis

Substances

  • Estrogen Receptor beta
  • GPER1 protein, human
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled