High circulating estrogens and selective expression of ERβ in prostate tumors of Americans: implications for racial disparity of prostate cancer

Although estrogen receptor beta (ER beta) has been implicated in prostate cancer (PCa) progression, its potential role in health disparity of PCa remains elusive. The objective of this study was to examine serum estrogens and prostate tumor ER beta expression and examine their correlation with clinical and pathological parameters in African American (AA) versus Caucasian American (CA) men. The circulating 17 beta-estradiol (E2) was measured by enzyme immunoassay in blood procured from racially stratified normal subjects and PCa patients. Differential expression profile analysis of ER beta was analyzed by quantitative immunohistochemistry using ethnicity-based tissue microarray encompassing 300 PCa tissue cores. In situ ER beta expression was validated by quantitative reverse transcription-PCR in matched microdissected normal prostate epithelium and tumor cells and datasets extracted from independent cohorts. In comparison with normal age-matched subjects, circulating E2 levels were significantly elevated in all PCa patients. Further analysis demonstrates an increase in blood E2 levels in AA men in both normal and PCa in comparison with age-and stage-matched counterparts of CA decent. Histochemical score analysis reveals intense nuclear immunoreactivity for ER beta in tumor cores of AA men than in CA men. Gene expression analysis in microdissected tumors corroborated the biracial differences in ER beta expression. Gene expression analysis from independent cohort datasets revealed correlation between ER beta expression and PCa progression. However, unlike in CA men, adjusted multivariate analysis showed that ER beta expression correlates with age at diagnosis and low prostate-specific antigen recurrence-free survival in AA men. Taken together, our results suggest that E2-ER beta axis may have potential clinical utility in PCa diagnosis and clinical outcome among AA men.