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

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 21; no. 9; pp. 1497 - 1509
• Main Authors: Pettersson, Andreas, Graff, Rebecca E., Bauer, Scott R., Pitt, Michael J., Lis, Rosina T., Stack, Edward C., Martin, Neil E., Kunz, Lauren, Penney, Kathryn L., Ligon, Azra H., Suppan, Catherine, Flavin, Richard, Sesso, Howard D., Rider, Jennifer R., Sweeney, Christopher, Stampfer, Meir J., Fiorentino, Michelangelo, Kantoff, Philip W., Sanda, Martin G., Giovannucci, Edward L., Ding, Eric L., Loda, Massimo, Mucci, Lorelei A.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2012
• Subjects: Aged; Biological and medical sciences; Cohort Studies; Gene Fusion; Gene Rearrangement; Humans; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - genetics; Neoplasm Staging; Nephrology. Urinary tract diseases; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Serine Endopeptidases - genetics; Trans-Activators - genetics; Transcriptional Regulator ERG; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urinary system disease; Prognosis; Prostate disease; Malignant tumor; Metaanalysis; Cancerology; Cohort study; C-Onc gene; Gene rearrangement; Evolution; Male genital diseases; Prostate cancer; Protooncogene; Public health; Cancer
• ISSN: 1055-9965; 1538-7755; 1538-7755
• DOI: 10.1158/1055-9965.EPI-12-0042

Background: Whether the genomic rearrangement transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (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 1,180 men treated with radical prostatectomy between 1983 and 2005. During a median follow-up of 12.6 years, 266 men experienced recurrence and 85 men developed lethal disease. We found no significant association between ERG overexpression and biochemical recurrence [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.78–1.26] or lethal disease (HR, 0.93; 95% CI, 0.61–1.43). The meta-analysis of prostatectomy series included 5,074 men followed for biochemical recurrence (1,623 events), and 2,049 men followed for lethal disease (131 events). TMPRSS2:ERG was associated with stage at diagnosis [risk ratio (RR)≥T3 vs. T2, 1.23; 95% CI, 1.16–1.30) but not with biochemical recurrence (RR, 1.00; 95% CI, 0.86–1.17) or lethal disease (RR, 0.99; 95% CI, 0.47–2.09). 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. Cancer Epidemiol Biomarkers Prev; 21(9); 1497–509. ©2012 AACR.