Abstract 1859: Potential impact on the biology and biomarker utility of ERG-typing in the context of ethnic differences of prostate cancer

Abstract

Abstract Introduction: In comparison to other ethnicities African American men have the highest incidence and mortality rates of prostate cancer (CaP). Recent reports on ethnic differences of ERG oncogenic activation, the most common CaP genomic alteration, provide new insights into the ERG based stratification of CaP in the context of the increasingly diverse ethnic patient populations in the United States. This rapidly advancing knowledge has potential to stratify CaP by ERG typing in a given patient population that may eventually lead to new targeted treatments. Methods: Whole-mounted prostate sections of 91 Caucasian American (CA) and 91 African American (AA) men matched for age, Gleason score and pathologic stage were analyzed for ERG oncoprotein expression. High grade tumors with a primary Gleason pattern of 4 or 5 or cumulative Gleason score of 8-10 from a total of 63 AA patients and 63 CA patients were also assessed for ERG. Hormone naïve AA CaP patients (n=306) with a minimum of two years of follow up after radical prostatectomy were evaluated for ERG frequencies in whole-mounted prostate specimens. Performance of PCA3, ERG and PSA biomarkers were evaluated in 306 post-DRE urine samples from CA and AA patients by the DTS® 400 system and by whole transcriptome analyses in selected CaP samples. The associations of biomarker scores with clinical parameters were assessed in matching biopsies and were stratified by ethnicity. Results: Remarkably higher frequencies of ERG expression was noted in the index tumors of CA (63.3%) compared to AA (28.6%) men. The observed difference was even more pronounced in higher grade disease AA (16%) and CA (49%), respectively. ERG positive tumors were more likely to be present in index tumors of younger AA men. Furthermore, ERG negative tumors were significantly associated with higher pathologic T stage. In urine assays the combination of ERG and PCA3 scores increased the AUC performance as compared to serum PSA alone (0.68 vs. 0.53, p = 0.0062) for predicting CaP in CA men. In contrast, the biomarker panel showed strikingly poor performance in AA men (AUC = 0.49). Conclusions: ERG-based stratification defines molecular subtypes and ethnic differences in the biology of CaP. Association of ERG negative status with high grade tumors and poor prognostic features in AA patients warrants the development of informative marker panels that includes ERG to aid in diagnostic, prognostic and targeted therapy settings. Citation Format: Albert Dobi, Yongmei Chen, Amina Ali, Denise Young, Philip Rosen, James Farrell, Michael Degon, Sudhir Srivastava, Jacob Kagan, Jocelyn Lee, Jennifer Cullen, Gyorgy Petrovics, David G. McLeod, Isabell A. Sesterhenn, Shiv Srivastava. Potential impact on the biology and biomarker utility of ERG-typing in the context of ethnic differences of prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1859. doi:10.1158/1538-7445.AM2014-1859