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• W1973368085 abstract "No AccessJournal of UrologyInvestigative Urology1 May 2010Clinical Implications of TMPRSS2-ERG Gene Fusion Expression in Patients With Prostate Cancer Treated With Radical Prostatectomy José Rubio-Briones, Antonio Fernández-Serra, Ana Calatrava, Zaida García-Casado, Luis Rubio, Miguel A. Bonillo, Inmaculada Iborra, Eduardo Solsona, and José A. López-Guerrero José Rubio-BrionesJosé Rubio-Briones Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain Equal study contribution. More articles by this author , Antonio Fernández-SerraAntonio Fernández-Serra Department of Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain Equal study contribution. More articles by this author , Ana CalatravaAna Calatrava Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author , Zaida García-CasadoZaida García-Casado Department of Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author , Luis RubioLuis Rubio Department of Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author , Miguel A. BonilloMiguel A. Bonillo Department of Urology, University Hospital La Fe, Valencia, Spain More articles by this author , Inmaculada IborraInmaculada Iborra Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author , Eduardo SolsonaEduardo Solsona Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author , and José A. López-GuerreroJosé A. López-Guerrero Department of Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.12.096AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Molecular prognostic factors may be useful tools for prostate cancer that complement classic clinicopathological factors. Genetic rearrangements between TMPRSS2 and ETS have been described for prostate cancer but their clinical significance is still unclear. We analyzed the association of the TMPRSS2-ERG fusion gene with prostate cancer outcome in patients treated with radical prostatectomy. Material and Methods: We analyzed prostate cancer samples from 226 patients treated with radical prostatectomy from 1996 to 2002 with a median followup of 84 months (range 9 to 153). TMPRSS2-ERG fusion gene expression was determined by reverse transcriptase-polymerase chain reaction. Clinicopathological and molecular variables were related to biochemical and clinical progression-free survival by the Kaplan-Meier proportional risk log rank test. A Cox proportional hazards model using stepwise selection was used to identify independent predictors of poor outcome. Results: TMPRSS2-ERG fusion was detected in 114 cases (50.4%). We noted no association between fusion gene status and prostate cancer clinicopathological characteristics. However, when patients were grouped by TMPRSS2-ERG fusion gene status, different clinicopathological prognostic factors defined each group for biochemical and clinical progression-free survival. Prostate specific antigen, specimen Gleason score and margin status were independent prognostic factors in patients with prostate cancer expressing the fusion gene. In the nonexpressing TMPRSS2-ERG group the prognostic factors were cT, Gleason score and margins. Conclusions: TMPRSS2-ERG fusion gene status classifies patients with prostate cancer treated with radical prostatectomy into groups defined by different prognostic factors. This could be the basis for designing more refined treatment strategies. References 1 : Long-term outcome among men with conservatively treated localised prostate cancer. Br J Cancer2006; 95: 1186. Google Scholar 2 : Primary cryotherapy with salvage external beam radiotherapy for locally recurrent prostate cancer. Clin Oncol (R Coll Radiol)2008; 20: 385. Google Scholar 3 : Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science2005; 310: 644. Google Scholar 4 : TMPRSS2: ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res2006; 66: 3396. Google Scholar 5 : ETS transcription factors: possible targets for cancer therapy. Cancer Sci2004; 95: 626. Google Scholar 6 : A second Ewing's sarcoma translocation, t (21; 22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet1994; 6: 146. Google Scholar 7 : ETS transcription factors and their emerging roles in human cancer. Eur J Cancer2005; 41: 2462. Google Scholar 8 : HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer. Oncogene1997; 15: 1513. Google Scholar 9 : The androgen-regulated type II serine protease TMPRSS2 is differentially expressed and mislocalized in prostate adenocarcinoma. J Pathol2008; 215: 118. Google Scholar 10 : ETS gene fusions in prostate cancer: from discovery to daily clinical practice. Eur Urol2009; 56: 275. Google Scholar 11 : Expression of TMPRSS2: ERG gene fusion in prostate cancer cells is an important prognostic factor for cancer progression. Cancer Biol Ther2007; 6: 40. Google Scholar 12 : Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Cancer Res2007; 67: 7991. Google Scholar 13 : Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues. Mod Pathol2007; 20: 921. Google Scholar 14 : Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer. BMC Cancer2008; 8: 230. Google Scholar 15 : TMPRSS2: ERG rearrangement is an independent marker of good prognosis in prostate cancer. Eur Urol2008; 7: 253. Google Scholar 16 : TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res2009; 69: 1400. Google Scholar 17 : Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis. Nat Genet2009; 41: 524. Google Scholar 18 : Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate. Nat Genet2009; 41: 619. Google Scholar 19 : Chromosomal abnormalities in cancer. N Engl J Med2008; 359: 722. Google Scholar 20 : Morphological features of TMPRSS2–ERG gene fusion prostate cancer. J Pathol2007; 212: 91. Google Scholar 21 : TMPRSS2: ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene2007; 26: 4596. Google Scholar 22 : Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod Pathol2007; 20: 538. Google Scholar 23 : TMPRSS2: ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res2006; 66: 8337. Google Scholar 24 : Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res2006; 66: 8347. Google Scholar 25 : Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene2008; 27: 253. Google Scholar 26 : Characterization of TMPRSS2-ETS gene aberrations in androgen-independent metastatic prostate cancer. Cancer Res2008; 68: 3584. Google Scholar 27 : Characterization of TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia and potential clinical implications. Clin Cancer Res2008; 14: 3380. Google Scholar 28 : Noninvasive detection of TMPRSS2: ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia2006; 8: 885. Google Scholar 29 : Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. Clin Cancer Res2007; 13: 5103. Google Scholar 30 : A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res2008; 68: 645. Google Scholar © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byAtala A (2018) Re: ERF Mutations Reveal a Balance of ETS Factors Controlling Prostate OncogenesisJournal of Urology, VOL. 200, NO. 1, (31-32), Online publication date: 1-Jul-2018.Atala A (2016) Re: Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor OutcomeJournal of Urology, VOL. 197, NO. 3 Part 1, (701-702), Online publication date: 1-Mar-2017.Taneja S (2018) Re: Associations of Luminal and Basal Subtyping of Prostate Cancer with Prognosis and Response to Androgen Deprivation TherapyJournal of Urology, VOL. 198, NO. 6, (1211-1211), Online publication date: 1-Dec-2017.Casanova-Salas I, Rubio-Briones J, Calatrava A, Mancarella C, Masiá E, Casanova J, Fernández-Serra A, Rubio L, Ramírez-Backhaus M, Armiñán A, Domínguez-Escrig J, Martínez F, García-Casado Z, Scotlandi K, Vicent M and López-Guerrero J (2018) Identification of miR-187 and miR-182 as Biomarkers of Early Diagnosis and Prognosis in Patients with Prostate Cancer Treated with Radical ProstatectomyJournal of Urology, VOL. 192, NO. 1, (252-259), Online publication date: 1-Jul-2014.Salagierski M and Schalken J (2018) Molecular Diagnosis of Prostate Cancer: PCA3 and TMPRSS2:ERG Gene FusionJournal of Urology, VOL. 187, NO. 3, (795-801), Online publication date: 1-Mar-2012.Zhao H, Coram M, Nolley R, Reese S, Young S and Peehl D (2018) Transcript Levels of Androgen Receptor Variant AR-V1 or AR-V7 Do Not Predict Recurrence in Patients with Prostate Cancer at Indeterminate Risk for ProgressionJournal of Urology, VOL. 188, NO. 6, (2158-2164), Online publication date: 1-Dec-2012. Volume 183Issue 5May 2010Page: 2054-2061 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.Keywordsprostateprostatectomygene fusionprognosisprostatic neoplasmsAcknowledgmentsMaria Garcia Flores, Tania Mazcuñan, Vanesa Perez and Laura Martinez provided technical assistance.MetricsAuthor Information José Rubio-Briones Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain Equal study contribution. More articles by this author Antonio Fernández-Serra Department of Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain Equal study contribution. More articles by this author Ana Calatrava Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author Zaida García-Casado Department of Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author Luis Rubio Department of Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author Miguel A. Bonillo Department of Urology, University Hospital La Fe, Valencia, Spain More articles by this author Inmaculada Iborra Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author Eduardo Solsona Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author José A. López-Guerrero Department of Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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