The Importance Of Estrogen-Er Beta Axis In Racial Disparity Of Prostate Cancer

Purpose: The role of estrogens and estrogen receptors (ERs) in the disproportionate incidence and mortality of prostate cancer (PCa) has not been established. Although ERβ has been implicated in PCa progression, its ethnic-based expression and underlying mechanisms are not fully understood. The aim of this study is to establish correlation between estrogen-ERβ axis and clinical outcome in African American (AA) in comparison to Caucasian American (CA) men. Patients and Methods: 17β-Estradiol (E2) was determined in the blood procured from normal (n=30) and PCa patients (n=50) by ELISA. The expression of ERβ was assessed using an NCI-designed ethnicity-based tissue microarray (TMA) slide encompassing 150 each of AA and CA PCa tissue cores, 17 BPH, 13 normal biopsies, and 3 PCa cell lines (LNCaP, DU-145 and PC-3). Validation of ERβ in situ was validated by qRT-PCR in matched microdissected tumors and normal glands from both populations. Results: In comparison to normal subjects, circulating E2 levels were significantly (p=0.0160) elevated in AA-men than in CA-men with PCa. Additionally, a significant difference in E2 blood levels (p=0.0015) was observed between AA and AA PCa patients. Histoscore analysis demonstrate intense nuclear immunoreactivity (p=0.0018) against ERβ in tumors of AA than CA men. This notion was further validated by qRT-PCR on LCM-procured tumor cells (p=0.0315). In the adjusted multivariate analysis there was no correlation between ERβ expression and any clinical parameters in PCa tissues. In AA, there was a positive correlation between Gleason score (GS) and age but a negative correlation was found between GS, age and PSA-recurrence free. However, no correlation was found in CA. Conclusion: Together, high circulating levels of blood estrogens and mRNA levels coupled with a differential expression of ERβ in PCa tissues suggest a potential role for estrogen-ERβ axis in the development of castrate-resistant prostate cancer in AA men. Key words: E2, ER beta, mRNA, TMA, histoscore, African Americans, health disparities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 438. doi:1538-7445.AM2012-438