title: Immunohistochemistry for ERG expression as a surrogate for TMPRSS2-ERG fusion detection in prostatic adenocarcinomas.
abstract: BACKGROUND
  TMPRSS2-ERG fusions have been identified in about one-half of all prostatic adenocarcinomas (PCas). Fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction have been the most commonly used techniques in this setting. The aim of this study was to evaluate the utility of ERG immunoexpression as a surrogate for TMPRSS2-ERG fusion in a large series of PCa cases.
  
  
  METHODS
  Four hundred twenty-seven radical retropubic prostatectomy tissue samples were used to construct 10 tissue microarrays (TMAs). FISH analysis was previously conducted using dual-color interphase break-apart probes for the 5' and 3' regions of the ERG gene. ERG expression was evaluated using a commercial rabbit anti-ERG monoclonal antibody (clone EPR3864; Epitomics, Burlingame, CA). Each TMA spot was independently assessed, and any nuclear staining positivity was considered as indicative of ERG expression.
  
  
  RESULTS
  TMPRSS2-ERG fusions were detected by FISH in 195 (45.7%) of the PCa cases. ERG immunoexpression was found in 192 (45.0%) of the PCa cases and in none of the nontumoral tissue samples. Mean ERG H-scores were significantly higher in tumors harboring FISH-detected TMPRSS2-ERG fusions (P<0.00001), and there was a strong association between ERG immunohistochemical expression and the TMPRSS2-ERG status defined by FISH (P<0.00001), with a sensitivity of 86% (95% CI, 80%-90%) and a specificity of 89% (95% CI, 84%-93%). Receiver-operating characteristic curve analysis showed that ERG immunoexpression had a high accuracy for identifying TMPRSS2-ERG fusions detected by FISH, with an area under the curve of 0.87 (95% CI, 0.84%-0.91; P<0.00001).
  
  
  CONCLUSIONS
  We found that ERG immunohistochemical expression has a high accuracy for defining the TMPRSS-ERG fusion status. ERG immunohistochemistry may offer an accurate, simpler, and less costly alternative for evaluation of ERG fusion status in PCa than FISH.
authors.affiliation: Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
authors.forename: Roula
authors.initials: R
authors.lastname: Albadine
authors.forename: Antoun
authors.initials: A
authors.lastname: Toubaji
authors.forename: Jessica
authors.initials: J
authors.lastname: Hicks
authors.forename: Alan
authors.initials: A
authors.lastname: Meeker
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012372:ROC Curve; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG