Relevance of cohort design for studying the frequency of the ERG rearrangement in prostate cancer

Histopathology. 2011 Jun;58(7):1028-36. doi: 10.1111/j.1365-2559.2011.03862.x.

Abstract

Aims: ERG rearrangements, mostly resulting in TMPRSS2-ERG fusions, are frequent alterations in prostate cancer (PCa), with a frequency ranging from 15% to 78%. As the reason for this variability is unknown, our aim was to investigate the ERG rearrangement frequency with a cohort design.

Methods and results: We assessed three well-defined cohorts for ERG rearrangements, using fluorescence in situ hybridization (FISH). The first cohort comprised 119 prostatectomy specimens. The second and third cohorts included incidentally diagnosed PCa [71 cystoprostatectomy specimens, and 105 transurethral resection of the prostate (TURP) specimens]. Seventy of 119 (59%) cases of the prostatectomy cohort harboured ERG rearrangements. Regarding zonal origin, 2/11 (18%) transition zone (TZ) foci and 75/145 (52%) peripheral zone (PZ) foci harboured ERG rearrangements. Within the cystoprostatectomies, 24/71 (34%) cases harboured ERG rearrangements. Regarding zonal origin, 2/9 (22%) TZ foci and 26/86 (30%) PZ foci harboured ERG rearrangements. PCa incidentally identified by TURP harboured ERG rearrangements in 31/105 (29%) cases.

Conclusions: ERG rearrangements occur in TZ PCa, although at a lower frequency than in PZ PCa. We confirmed that approximately half of all prostatectomies harbour ERG rearrangements. However, the frequency in incidentally diagnosed PCa cohorts was significantly lower, even if multifocality was considered. Consequently, zonal origin and cohort design are key for studying the clinical implications of ERG rearrangements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Cohort Studies
  • Gene Fusion
  • Gene Rearrangement*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Oncogene Proteins, Fusion / genetics
  • Prostatectomy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Research Design
  • Serine Endopeptidases / genetics
  • Trans-Activators / genetics*
  • Transcriptional Regulator ERG

Substances

  • ERG protein, human
  • Oncogene Proteins, Fusion
  • TMPRSS2-ERG fusion protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Serine Endopeptidases
  • TMPRSS2 protein, human