Title | The TMPRSS2:ERG fusion and response to androgen deprivation therapy for prostate cancer. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Graff RE, Pettersson A, Lis RT, DuPre N, Jordahl KM, Nuttall E, Rider JR, Fiorentino M, Sesso HD, Kenfield SA, Loda M, Giovannucci EL, Rosner B, Nguyen PL, Sweeney CJ, Mucci LA |
Corporate Authors | Transdisciplinary Prostate Cancer Partnership ToPCaP |
Journal | Prostate |
Volume | 75 |
Issue | 9 |
Pagination | 897-906 |
Date Published | 2015 Jun 15 |
ISSN | 1097-0045 |
Keywords | Aged, Cohort Studies, Follow-Up Studies, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasms, Hormone-Dependent, Nonsteroidal Anti-Androgens, Oncogene Proteins, Fusion, Proportional Hazards Models, Prospective Studies, Prostatic Neoplasms, Surveys and Questionnaires, Survival Analysis |
Abstract | BACKGROUND: In the United States, half of men with prostate cancer harbor the androgen-regulated gene fusion TMPRSS2:ERG. We hypothesized that men with TMPRSS2:ERG positive tumors are more responsive to androgen deprivation therapy (ADT). METHODS: We studied a cohort of 239 men with prostate cancer from the Physicians' Health Study and Health Professionals Follow-up Study who received ADT during their disease course. Fusion status was assessed on available tumor tissue by immunohistochemistry for ERG protein expression. We used Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for assessment of prostate cancer-specific mortality after ADT initiation. RESULTS: Roughly half of the men had stage T3 or higher tumors at diagnosis and 39% had Gleason 8-10 tumors. During an average follow up of 10.2 years, 42 men died from prostate cancer. There was a non-significant inverse association between positive fusion status and time to death from prostate cancer after ADT (multivariable HR: 0.76; 95% CI: 0.40-1.45). Harboring the TMPRSS2:ERG fusion was associated with a statistically significant lower risk of prostate cancer mortality among men who were treated with orchiectomy (multivariable HR: 0.13; 95% CI: 0.03-0.62), based on 15 events. CONCLUSIONS: Our results, combined with those from earlier studies, provide suggestive evidence that men with TMPRSS2:ERG positive tumors may have longer prostate cancer survival after ADT. Larger cohorts are needed for more robust results and to assess whether men with tumors harboring the fusion benefit from treatment with ADT in the (neo) adjuvant or metastatic setting specifically. |
DOI | 10.1002/pros.22973 |
Alternate Journal | Prostate |
PubMed ID | 25728532 |
PubMed Central ID | PMC4424159 |
Grant List | P50 CA090381 / CA / NCI NIH HHS / United States CA136578 / CA / NCI NIH HHS / United States P01 CA055075 / CA / NCI NIH HHS / United States CA141298 / CA / NCI NIH HHS / United States R01 HL034595 / HL / NHLBI NIH HHS / United States UM1CA167552 / CA / NCI NIH HHS / United States 5P50CA090381 / CA / NCI NIH HHS / United States R25 CA098566 / CA / NCI NIH HHS / United States R01 CA034944-03 / CA / NCI NIH HHS / United States CA097193 / CA / NCI NIH HHS / United States R25 CA112355 / CA / NCI NIH HHS / United States U01 CA098233 / CA / NCI NIH HHS / United States R01 HL026490 / HL / NHLBI NIH HHS / United States UM1 CA167552 / CA / NCI NIH HHS / United States R01 HL034595-07 / HL / NHLBI NIH HHS / United States R01 CA040360 / CA / NCI NIH HHS / United States R01 CA136578 / CA / NCI NIH HHS / United States R01 HL026490-03 / HL / NHLBI NIH HHS / United States R01 CA097193 / CA / NCI NIH HHS / United States U01CA098233 / CA / NCI NIH HHS / United States CA40360 / CA / NCI NIH HHS / United States R01 CA034944 / CA / NCI NIH HHS / United States R01 CA141298 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.