title: TMPRSS2:ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia.
abstract: OBJECTIVE
  High-grade prostatic intraepithelial neoplasia (HGPIN) is considered a precursor lesion of prostate cancer (PCa). The predictive value of ERG gene fusion in HGPIN for PCa was interrogated as a post hoc analysis in the context of a randomized clinical trial.
  
  
  METHODS
  The GTx Protocol G300104 randomly assigned 1,590 men with biopsy-diagnosed HGPIN to receive toremifene or placebo for 3 years or until a diagnosis of PCa was made on prostate biopsy. As part of this phase III clinical trial, a central pathologist evaluated biopsies of patients with isolated HGPIN at baseline and 12, 24, and 36 months of follow-up. ERG immunohistochemistry was performed on biopsies from 461 patients and evaluated for protein overexpression.
  
  
  RESULTS
  ERG expression was detected in 11.1% of patients (51 of 461 patients) with isolated HGPIN. In the first year and during the 3-year clinical trial, 14.7% and 36.9% of 461 patients were diagnosed with PCa, respectively. Patients with ERG expression were more likely to develop PCa, with 27 (53%) of 51 ERG-positive and 143 (35%) of 410 ERG-negative patients experiencing progression to PCa (P = .014, Fisher's exact test). ERG expression was not associated with age, baseline PSA, Gleason score, or tumor volume.
  
  
  CONCLUSIONS
  This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression. Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification.
authors.affiliation: Kyung Park, Christopher E. Barbieri, and Mark A. Rubin, Weill Medical College of Cornell University, New York, NY; James T. Dalton, Ramesh Narayanan, Michael L. Hancock, and Mitchell S. Steiner, GTx, Memphis, TN; and David G. Bostwick, Bostwick Laboratories, Glen Allen, VA.
authors.forename: Kyung
authors.initials: K
authors.lastname: Park
authors.forename: James T
authors.initials: JT
authors.lastname: Dalton
authors.forename: Ramesh
authors.initials: R
authors.lastname: Narayanan
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Barbieri
authors.forename: Michael L
authors.initials: ML
authors.lastname: Hancock
authors.forename: David G
authors.initials: DG
authors.lastname: Bostwick
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Steiner
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D019048:Prostatic Intraepithelial Neoplasia / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017312:Toremifene / Q000627:therapeutic use*; D015854:Up-Regulation
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D017312:Toremifene