title: ERG overexpression and multifocality predict prostate cancer in subsequent biopsy for patients with high-grade prostatic intraepithelial neoplasia.
abstract: OBJECTIVE
  The most important clinical significance of an isolated high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis is the risk of missed prostate cancer (PCa) in subsequent biopsies. Because most patients with HGPIN do not harbor or develop PCa, clinical, pathological, or molecular markers that predict of PCa risk are of clinical significance.
  
  
  METHODS
  Overall, 155 men with a diagnosis of isolated HGPIN, which was based on the results of extended biopsy, and who underwent at least one repeat biopsy were analyzed for ERG oncoprotein (ERG) expression and clinicopathological parameters to determine the risk of finding PCa in subsequent biopsies.
  
  
  RESULTS
  Of 155 patients diagnosed with HGPIN on initial biopsy, 39 (25%) had PCa on subsequent biopsies. For men with only one repeat biopsy, the cancer detection rate was 22%. Most (54%) PCas were detected in≤6 months of rebiopsy. ERG expression was present in 15 patients with HGPIN (9.6%). Patients with ERG expression in HGPIN were more likely to have PCa in repeat biopsy, with 9 (60%) ERG-positive and 30 (21%) of ERG-negative patients having PCa (P = 0.001). Multifocal involvement (P = 0.0001), cribriform morphology (P = 0.004), and bilaterality (P = 0.0075) of HGPIN were other significant risk factors. On multivariable analysis, only the presence of ERG positivity and multifocality remained significant parameters in detecting PCa on a repeat biopsy. The presence of ERG-negative focal HGPIN involving one core, which accounted for 46% of patients, had minimal (16%) PCa risk on subsequent biopsy. In total, 8 patients (89%) ERG-positive HGPIN had PCa identified at identical sites on subsequent biopsy, of which 5 (71%) were ERG positive.
  
  
  CONCLUSIONS
  The status of ERG expression in HGPIN along with other histological parameters stratifies patients into low- and high-risk groups for having PCa on subsequent biopsy. Our results further support molecular characterization of HGPIN as a means to improve risk stratification and optimize surveillance strategies.
authors.affiliation: Division of Urologic Pathology, Miraca Life Sciences Research Institute, Miraca Life Sciences, Irving, TX. Electronic address: rshah@Miracals.com.
authors.forename: Rajal B
authors.initials: RB
authors.lastname: Shah
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Urology, The University of Texas at Houston, Houston, TX.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Dhanani
authors.affiliation: Division of Urologic Pathology, Miraca Life Sciences Research Institute, Miraca Life Sciences, Irving, TX.
authors.forename: Savvas
authors.initials: S
authors.lastname: Mendrinos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D019048:Prostatic Intraepithelial Neoplasia / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D000071230:Transcriptional Regulator ERG / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; D000071230:Transcriptional Regulator ERG
keywords: ERG; High-grade prostatic intraepithelial neoplasia (HGPIN); Multifocality; Prostate cancer