title: Prevalence of TMPRSS2-ERG fusion prostate cancer among men undergoing prostate biopsy in the United States.
abstract: OBJECTIVE
  Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in samples of transurethral resection of the prostate from a Swedish cohort of patients with incidental prostate cancer followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among prostate-specific antigen-screened men undergoing prostate biopsy in the United States.
  
  
  METHODS
  We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a fluorescent in situ hybridization assay. One hundred and thirty-four samples (100 cancer and 34 benign) were assessable.
  
  
  RESULTS
  ERG gene rearrangement was detected in 46% of prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (P < 0.0001). Evaluation of morphologic features showed that cribriform growth, blue-tinged mucin, macronucleoli, and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion-positive prostate cancer biopsies than gene fusion-negative prostate cancer biopsies (P < or = 0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (P = 0.02).
  
  
  CONCLUSIONS
  This is the first prospective North American multicenter study to characterize TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphologic features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and a need for the development of noninvasive screening tests to detect TMPRSS2-ERG rearrangement.
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Juan-Miguel
authors: JM
authors: Mosquera
authors: Rohit
authors: R
authors: Mehra
authors: Meredith M
authors: MM
authors: Regan
authors: Sven
authors: S
authors: Perner
authors: Elizabeth M
authors: EM
authors: Genega
authors: Gerri
authors: G
authors: Bueti
authors: Rajal B
authors: RB
authors: Shah
authors: Sandra
authors: S
authors: Gaston
authors: Scott A
authors: SA
authors: Tomlins
authors: John T
authors: JT
authors: Wei
authors: Michael C
authors: MC
authors: Kearney
authors: Laura A
authors: LA
authors: Johnson
authors: Jeffrey M
authors: JM
authors: Tang
authors: Arul M
authors: AM
authors: Chinnaiyan
authors: Mark A
authors: MA
authors: Rubin
authors: Martin G
authors: MG
authors: Sanda
mesh_terms: D000368:Aged; D001706:Biopsy; D005787:Gene Frequency; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011446:Prospective Studies; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012697:Serine Endopeptidases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D014481:United States
chemical_list: C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; D017430:Prostate-Specific Antigen