title: Relevance of cohort design for studying the frequency of the ERG rearrangement in prostate cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Institute of Pathology, Comprehensive Cancer Centre, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.forename: Veit J
authors.initials: VJ
authors.lastname: Scheble
authors.forename: Roopika
authors.initials: R
authors.lastname: Menon
authors.forename: Gregor
authors.initials: G
authors.lastname: Scharf
authors.forename: Theresia
authors.initials: T
authors.lastname: Wilbertz
authors.forename: Karen
authors.initials: K
authors.lastname: Petersen
authors.forename: Christine
authors.initials: C
authors.lastname: Beschorner
authors.forename: Markus
authors.initials: M
authors.lastname: Reischl
authors.forename: Rainer
authors.initials: R
authors.lastname: Kuefer
authors.forename: David
authors.initials: D
authors.lastname: Schilling
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012107:Research Design; D012697:Serine Endopeptidases / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human