The TMPRSS2:ERG Rearrangement, ERG Expression, and Prostate Cancer Outcomes: a Cohort Study and Meta-analysis

Background: Whether the genomic rearrangement TMPRSS2:ERG has prognostic value in prostate cancer is unclear. Methods: Among men with prostate cancer in the prospective Physicians' Health and Health Professionals Follow-Up Studies, we identified rearrangement status by immunohistochemical assessment of ERG protein expression. We used Cox models to examine associations of ERG overexpression with biochemical recurrence and lethal disease (distant metastases or cancer-specific mortality). In a meta-analysis including 47 additional studies, we used random effects models to estimate associations between rearrangement status and outcomes. Results: The cohort consisted of 1,052 men treated with radical prostatectomy between 1982 and 2005. During a median follow-up of 12.5 years, 245 men experienced recurrence, and 95 men developed lethal disease. We found no significant association between ERG overexpression and biochemical recurrence (HR: 0.93; 95% CI: 0.72-1.19) or lethal disease (HR: 0.81; 95% CI: 0.54-1.21). The meta-analysis of prostatectomy series included 4,946 men followed for biochemical recurrence (1,602 events), and 1,921 men followed for lethal disease (141 events). TMPRSS2:ERG was associated with stage at diagnosis (RR≥T3 vs. T2: 1.22; 95% CI: 1.15-1.29) but not with biochemical recurrence (RR: 1.00; 95% CI: 0.86-1.17) or lethal disease (RR: 0.93; 95% CI: 0.43-1.99). Conclusions: These results suggest that TMPRSS2:ERG , or ERG overexpression, is associated with tumor stage but does not strongly predict recurrence or mortality among men treated with radical prostatectomy. Impact: This is the largest prospective cohort study to examine associations of ERG overexpression and lethal prostate cancer among men treated with radical prostatectomy.