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.
Written by:
Pettersson A, Graff RE, Bauer SR, Pitt MJ, Lis RT, Stack EC, Martin NE, Kunz L, Penney KL, Ligon A, Suppan C, Flavin R, Sesso H, Rider JR, Sweeney CS, Stampfer MJ, Fiorentino M, Kantoff PW, Sanda MG, Giovannucci E, Ding EL, Loda M, Mucci LA. Are you the author?
Department of Epidemiology, Harvard School of Public Health.
Reference: Cancer Epidemiol Biomarkers Prev. 2012 Jun 26. Epub ahead of print.
doi: 10.1158/1055-9965.EPI-12-0042
PubMed Abstract
PMID: 22736790
UroToday.com Prostate Cancer Section