Racial/ethnic variation in a common genetic alteration in prostate cancer.

Abstract

14 Background: The molecular basis of racial/ethnic differences in the detection and outcomes of the carcinoma of the prostate (CaP) needs to be better defined to improve biomarkers and identify appropriate therapeutic targets. ETS-related gene fusions in proto-oncogenes (ERG, ETV1) are among the most common early oncogenic alterations described in CaP. Studies have highlighted the racial/ethnic variation in ERG fusion and ERG oncoprotein expression frequencies showing: the highest frequencies in Caucasian (CA) men, the lowest frequencies in Asian men, and intermediate frequencies in African American (AA) men. These differences persisted when patients were carefully matched for age and clinico-pathologic features. Building on previous work, the current study was conducted to evaluate ERG expression frequencies in a large cohort of AA and CA CaP patients. Methods: Patients enrolled at the Walter Reed National Military Medical Center who consented to provide radical prostatectomy (RP) specimens to the CPDR Tissue Bank and Clinical Database were evaluated. The current study included 443 AA and 696 CA patients. ERG oncoprotein expression was detected by immunohistochemistry using the 9FY mouse monoclonal anti-ERG antibody and was correlated with clinico-pathologic features and CaP outcomes. Results: Lower frequencies of ERG in the index tumors of AA men as compared to CA men (28.4% vs. 51.5%, p < 0.0001) were observed. Furthermore, AA men with higher grade CaP (Gleason 8-10) had even lower ERG frequency (16%), suggesting distinct molecular biologic features in aggressive CaP for AA men. A trend with age was observed for both racial groups, with younger CA showing higher ERG frequencies. At least one focus of ERG positive PIN was present in prostates with ERG positive tumors. In both CA and AA patients, a very low frequency (8%) of ERG expression was noted in anterior index tumors compared to posterior tumors. Conclusions: This study lends increasing support to differences of the most common early genomic alteration (ERG) between AA and CA CaP patients. The study also underscores the importance of identifying new or improving existing biomarkers with consideration of patient race/ethnicity.