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

Cancer Epidemiology Biomarkers and Prevention - Tập 21 Số 9 - Trang 1497-1509 - 2012
Andreas Pettersson1,2,3,4,5,6,7, Rebecca E. Graff1,2,3,4,5,6,7, Scott R. Bauer1,2,3,4,5,6,7, Michael J. Pitt1,2,3,4,5,6,7, Rosina T. Lis1,2,3,4,5,6,7, Edward C. Stack1,2,3,4,5,6,7, Neil E. Martin1,2,3,4,5,6,7, Lauren Kunz1,2,3,4,5,6,7,8, Kathryn L. Penney1,2,3,4,5,6,7, Azra H. Ligon1,2,3,4,5,6,7, Catherine Suppan1,2,3,4,5,6,7,8, Richard Flavin1,2,3,4,5,6,7, Howard D. Sesso1,2,3,4,5,6,7,8, Jennifer R. Rider1,2,3,4,5,6,7, Christopher Sweeney1,2,3,4,5,6,7,8, Meir J. Stampfer1,3,4,5,6,7, Michelangelo Fiorentino1,3,4,5,6,7, Philip W. Kantoff1,2,3,4,5,6,7,8, Martin G. Sanda1,2,3,4,5,6,7,8, Edward L. Giovannucci1,3,4,5,6,7, Eric L. Ding1,2,3,4,5,6,7, Massimo Loda1,2,3,4,5,6,7, Lorelei A. Mucci1,2,3,4,5,6,7
1Authors' Affiliations: 1Channing Laboratory, Department of Medicine, 2Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of 3Epidemiology, 4Biostatistics, and 5Nutrition, Harvard School of Public Health; 6Department of Pathology, Brigham and Women's Hospital; 7Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute; 8Department of Radiation Oncology, Dana-Farber Cancer Institute; 9Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School; 10Department of Surgery–Division of Urology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; 11Department of Medicine, University of California San Francisco, San Francisco, California; 12Department of Pathology, National University of Ireland, Galway, Galway, Ireland; and 13Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy
2Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute
3Department of Medicine, University of California, San Francisco, San Francisco, California
4Department of Pathology, Brigham and Women's Hospital
5Department of Pathology, National University of Ireland, Galway, Galway, Ireland
6Department of Radiation Oncology, Dana-Farber Cancer Institute
7Departments of Epidemiology, Biostatistics, and Nutrition, Harvard School of Public Health
8Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy

Tóm tắt

Abstract 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.

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Cancer Epidemiology Biomarkers and Prevention

Tập 21 Số 9

1497-1509

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