Abstract A29: The TMPRSS2:ERG gene fusion, ERG expression and prostate cancer outcomes: A cohort study and meta-analysis

Abstract

Abstract Background: The TMPRSS2:ERG gene fusion is a common genomic abnormality in prostate cancer that has been studied as a possible biomarker of prognosis. Methods: We undertook a prospective cohort study and meta-analysis to evaluate whether TMPRSS2:ERG is associated with more aggressive prostate cancers. The cohort consisted of 1,052 men with prostate cancer treated by radical prostatectomy between 1982 and 2005 nested within the Physicians' Health Study and Health Professionals Follow-Up Study. We identified presence of the fusion by immunohistochemical assessment of ERG protein expression. We used Cox proportional hazards models for associations of the fusion with biochemical recurrence and lethal prostate cancer. The meta-analysis included 6,448 subjects with prostate cancer from 43 studies (including our cohort) published since 2005. Studies characterized presence of the fusion by fluorescence in situ hybridization, polymerase chain reaction, or immunohistochemistry. Results: During a median follow-up of 12.5 years, 245 men in the cohort experienced biochemical recurrence, and 95 developed lethal disease (distant metastases or cancer-specific mortality). Men whose tumors harbored the fusion were more likely to be diagnosed at a higher stage (p=0.02). There was no association, however, between the fusion and Gleason score (Gleason 8–10 vs. 2–6; p=0.45), biochemical recurrence (HR: 0.93; 95% CI: 0.72–1.20), and lethal disease (HR: 0.81; 95% CI: 0.54–1.22). For men treated with radical prostatectomy, the meta-analysis yielded similar results. Fusion status was associated with higher stage at diagnosis (RR: 1.19; 95% CI: 1.11–1.28), but not with Gleason score (RR: 0.91; 95% CI: 0.76–1.10), biochemical recurrence (RR: 1.01; 95% CI: 0.84–1.22) or lethal disease (RR: 0.93; 95% CI: 0.44–1.99). Conclusions: The results suggest that TMPRSS2:ERG fusion status and ERG expression are associated with higher stage at diagnosis but are not strong predictors of Gleason score, biochemical recurrence or cancer-specific death among men with prostate cancer treated with radical prostatectomy. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A29.