81 Background: Despite increasing recognition of molecular differences in prostate cancers from African-American men (AAM) and European-American men (EAM), the prognostic utility of novel tissue biomarkers in AAM remains poorly defined. Overexpression of the oncogenic transcriptional regulator EZH2 has been associated with clinical outcome in localized prostate cancer, but it has not been adequately evaluated in AAM. We sought to define the prognostic significance of EZH2 overexpression in a racially-balanced cohort of men with localized prostate cancer and to explore potential race-specific differences. Methods: This was a retrospective analysis of men who underwent radical prostatectomy at the University of Pennsylvania between 1991 and 2010. Subjects with formalin fixed paraffin embedded tissue available for EZH2 immunohistochemistry were included. Slides were graded in a semi-quantitative manner for both the volume and the intensity of EZH2 staining. Multivariate Cox regression models were used to evaluate the independent association of clinicopathologic parameters, including EZH2 staining index, and biochemical recurrence (BCR)-free survival. Results: 121 patients (62 AAM, 59 EAM) were eligible for analysis. 56 patients (46.3%) demonstrated EZH2 overexpression, which was balanced between AAM and EAM subgroups (43.6% vs 49.2%, respectively). Extracapsular extension, positive surgical margins, and EZH2 overexpression were independently associated with BCR-free survival (HR of 2.02 for EZH2 overexpression, 95% CI 1.05 – 3.86, p = 0.035). Potential effect modification by race was identified (p for interaction = 0.056). While EZH2 overexpression was independently associated with BCR-free survival in AAM (HR 2.78, 95% CI 1.06 – 7.32, p = 0.038), no significant association was identified in the EAM subset (HR 0.89, 95% CI 0.35 – 2.29, p = 0.812). Conclusions: EZH2 overexpression is a valid prognostic marker in AAM treated with prostatectomy. The potential for enhanced prognostic significance of EZH2 overexpression in AAM may lend insight into observed racial disparities. These results highlight the need for adequate representation of AAM in clinical trials evaluating novel EZH2-directed therapies.
RNA-seq profile of African American men with a clinically localized prostate cancer