title: TMPRSS2-ERG fusion heterogeneity in multifocal prostate cancer: clinical and biologic implications.
abstract: OBJECTIVE
  To characterize the clonality of TMPRSS2-ERG fusion in multifocal prostate cancer.
  
  
  METHODS
  From 80 consecutive radical prostatectomy specimens, we identified 32 cases with multiple spatially separate tumors. In each case, we assessed two to three tumor foci for TMPRSS2-ERG fusion using an ERG break-apart interphase fluorescence in situ hybridization assay.
  
  
  RESULTS
  Individual tumor foci showed homogeneity for fusion status (intrafocal clonal homogeneity). In 19 (59%) of the 32 cases, all foci within a case had the same fusion status (interfocal homogeneity). In 15 (80%) of the 19 cases, no foci had fusion, and in 4 (20%), all foci had fusion. Of the 32 cases, 13 (41%) demonstrated heterogeneity for fusion status within a case (interfocal clonal heterogeneity).
  
  
  CONCLUSIONS
  In this study, we have demonstrated interfocal heterogeneity and intrafocal homogeneity for TMPRSS2-ERG fusion in prostate cancer with multiple tumors. These findings support the multiclonal nature of prostate cancer with clinical implications for needle biopsy strategies and the development of urine-based screening tests.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Barry
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D001707:Biopsy, Needle; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000652:urine; D050939:Gene Fusion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics* / Q000652:urine; D015534:Trans-Activators / Q000235:genetics* / Q000652:urine; D000071230:Transcriptional Regulator ERG
chemical_list: D004268:DNA-Binding Proteins; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human