Abstract C18: ERG-focused evaluations of prostate cancer of African American men and its potential impact on utility in biomarker development and in enhanced personalized medicine

Abstract

Abstract Introduction: Prostate cancer incidence and associated mortality is highest in African American men in comparison to other ethnicities. The observed differences in incidence and disease aggressiveness at presentation support a potential role for different biochemical pathways of prostate carcinogenesis between African American and Caucasian men. Emerging observations of the ethnic differences of the ERG oncogenic activation, the most common prostate cancer genomic alteration described in Western countries, provides new insights into the ERG based stratification of prostate cancers in the context of the increasingly diverse ethnic patient populations in The United States. This rapidly advancing knowledge has potential to stratify prostate cancers by ERG typing in a given patient population that may eventually lead to new targeted treatments. Experimental procedures: For the comparative evaluation of ERG frequencies, ERG oncoprotein expression was analyzed in whole-mounted sections of 91 Caucasian American and 91 African American prostate cancer cases matched for age, Gleason score and pathologic stage. To evaluate the association of high grade tumors with ERG status prostate cancer specimens with a primary Gleason pattern of 4 or 5 or cumulative Gleason score of 8-10 from a total of 63 African American patients and 63 Caucasian American patients matched for age. For the comprehensive evaluation of ERG frequencies in African American patients we have examined 306 whole mounted prostate specimens representing hormone naïve cases with a minimum of two years of follow up after radical prostatectomy. ERG oncoprotein was evaluated by immunohistochemistry in all cases and the genomic rearrangement of the ERG gene was assessed in selected cases by FISH assy. Results: Markedly greater frequencies of ERG oncoprotein expression was noted in the index tumors of the Caucasian Americans (63.3%) compared to the African Americans (28.6%). The observed difference was even more pronounced in higher grade disease indicating significantly lower ERG frequencies among African American (16%) patients in comparison to Caucasian American men (49%). Comprehensive evaluation of ERG frequencies revealed that ERG positive tumors were more likely to be present in index tumors of younger African American men, whereas, ERG negative tumors were significantly associated with higher pathologic T stage when all tumors were assessed. Conclusions: ERG-based stratification defines molecular subtypes of prostate cancers. Association of ERG negative status with high grade tumors and poor prognostic features in African American patients warrants the development of informative marker panels that includes ERG to aid in diagnostic, prognostic and targeted therapy settings. The results of the present study underscore that typing prostate cancers for ERG significantly contributes to the understanding of causal alterations resulting in higher incidence and associated mortality among African American prostate cancer patients. Citation Format: Albert Dobi, Philip Rosen, James Farrell, Michael Degon, Denise Young, Sudhir Srivastava, Jacob Kagan, Gyorgy Petrovics, Jennifer Cullen, David G. McLeod, Isabell A. Sesterhenn, Shiv Srivastava. ERG-focused evaluations of prostate cancer of African American men and its potential impact on utility in biomarker development and in enhanced personalized medicine. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C18. doi:10.1158/1538-7755.DISP13-C18