The Increased Frequency of ERG Oncoprotein Expression in High Grade Prostate Cancer in Caucasian American Compared to African American Men
James Farrell, Denise Young, Gyorgy Petrovics, Yongmei Chen, Jennifer Cullen, Albert Dobi, David G McLeod, Shiv Srivastava, Isabell Sesterhenn. Center for Prostate Disease Research, Bethesda, MD; Walter Reed National Military Medical Center, Bethesda, MD; Joint Pathology Center, Silver Spring, MD
Background: TMPRSS2-ERG fusion leading to ERG protein expression is a common oncogenic alteration in prostate cancer (CaP). Prior studies from our and other groups suggested that it is more common in Caucasian American (CA) than in African Americans (AA) CaP. Further, high grade disease showed much lower ERG frequency in AA CaP, but this needs to be validated in a larger cohort. Therefore, we sought to determine the association between race and ERG expression in a cohort of high grade CaP. We examined whether the prevalence of ERG has prognostic significance for CaP disease-specific outcomes.
Design: CaP patients with a Gleason score of 8-10 were included as well as patients with a primary Gleason pattern 4 or 5. Sixty three AA patients were age-matched with 63 CA patients (n=126). Immunohistochemistry was performed to detect fusion status in representative whole mount sections of prostatectomies using the ERG monoclonal antibody 9FY. Chi-squared tests were performed for descriptive statistics. Multivariate analysis and Kaplan-Meier curves were used to evaluate the clinical significance of ERG oncoprotein positivity.
Results: The frequency of ERG-positive index tumors in high grade CaP was significantly greater among CA patients compared to AA patients (49% vs.16%, P < .0001) by chi-squared analysis. This observation persisted when all ERG-positive tumor foci were assessed between CA and AA patients (59% vs. 33%, P = .0042). Neither ERG prevalence nor race was predictive of biochemical recurrence in this cohort.
Conclusions: In this study the prevalence of ERG oncoprotein expression (predominantly due to TMPRSS2-ERG gene fusion) in high grade CaP patients stratified by race is significantly more common in high grade CaP of CA compared with AA patients. Genetic alterations in high grade CaP in the AA population need to be further determined. This study underscores that typing of prostate tumors for ERG may enhance our understanding of biological differences between ethnic groups.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 146, Monday Afternoon