TMPRSS2-ERG status is not prognostic following prostate cancer radiotherapy: Implications for fusion status anddsb repair

Alan Dal Pra, Emilie Lalonde, Jenna Sykes, Fiona Warde, Adrian Ishkanian, Alice Meng, Chad Maloff, John Srigley, Anthony M. Joshua, Gyorgy Petrovics, Theodorus Van Der Kwast, Andrew Evans, Michael Milosevic, Fred Saad, Colin Collins, Jeremy Squire, Wan Lam, Tarek A. Bismar, Paul C. Boutros, Robert G. Bristow

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Background: Preclinical data suggest that TMPRSS2-ERG gene fusions, present in about 50% of prostate cancers, may be a surrogate for DNA repair status and therefore a biomarker for DNA-damaging agents. To test this hypothesis, we examined whether TMPRSS2-ERG status was associated with biochemical failure after clinical induction of DNA damage following image-guided radiotherapy (IGRT). Methods: Pretreatment biopsies from two cohorts of patients with intermediate-risk prostate cancer [T1/T2, Gleason score (GS) < 8, prostate-specific antigen (PSA) < 20 ng/mL; >7 years follow-up] were analyzed: (i) 126 patients [comparative genomic hybridization (CGH) cohort] with DNA samples assayed by array CGH (aCGH) for the TMPRSS2-ERG fusion; and (ii) 118 patients [immunohistochemical (IHC) cohort] whose biopsy samples were scored within a defined tissue microarray (TMA) immunostained for ERG overexpression (known surrogate for TMPRSS2-ERG fusion). Patients were treated with IGRT with a median dose of 76 Gy. The potential role of TMPRSS2-ERG status as a prognostic factor for biochemical relapse-free rate (bRFR; nadir p 2 ng/mL) was evaluated in the context of clinical prognostic factors in multivariate analyses using a Cox proportional hazards model. Results: TMPRSS2-ERG fusion by aCGH was identified in 27 (21%) of the cases in the CGH cohort, and ERG overexpression was found in 59 (50%) patients in the IHC cohort. In both cohorts, TMPRSS2-ERG status was not associated with bRFR on univariate or multivariate analysis. Conclusions: In two similarly treated IGRT cohorts, TMPRSS2-ERG status was not prognostic for bRFR, in disagreement with the hypothesis that these prostate cancers have DNA repair defects that render them clinically more radiosensitive. TMPRSS2-ERG is therefore unlikely to be a predictive factor for IGRT response.

Original languageEnglish (US)
Pages (from-to)5202-5209
Number of pages8
JournalClinical Cancer Research
Volume19
Issue number18
DOIs
StatePublished - Sep 15 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Pra, A. D., Lalonde, E., Sykes, J., Warde, F., Ishkanian, A., Meng, A., Maloff, C., Srigley, J., Joshua, A. M., Petrovics, G., Van Der Kwast, T., Evans, A., Milosevic, M., Saad, F., Collins, C., Squire, J., Lam, W., Bismar, T. A., Boutros, P. C., & Bristow, R. G. (2013). TMPRSS2-ERG status is not prognostic following prostate cancer radiotherapy: Implications for fusion status anddsb repair. Clinical Cancer Research, 19(18), 5202-5209. https://doi.org/10.1158/1078-0432.CCR-13-1049