TMPRSS2-ERG fusion heterogeneity in multifocal prostate cancer: clinical and biologic implications

Urology. 2007 Oct;70(4):630-3. doi: 10.1016/j.urology.2007.08.032.


Objectives: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biopsy, Needle
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / urine
  • Gene Fusion*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Neoplasms, Multiple Primary / diagnosis
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Serine Endopeptidases / genetics*
  • Serine Endopeptidases / urine
  • Trans-Activators / genetics*
  • Trans-Activators / urine
  • Transcriptional Regulator ERG


  • DNA-Binding Proteins
  • ERG protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Serine Endopeptidases
  • TMPRSS2 protein, human