title: Frequent discordance between ERG gene rearrangement and ERG protein expression in a rapid autopsy cohort of patients with lethal, metastatic, castration-resistant prostate cancer.
abstract: BACKGROUND
  ERG rearrangements in localized prostate cancer can be detected with high sensitivity and specificity by immunohistochemistry (IHC). However, recent data suggest that ERG IHC may be less sensitive for ERG rearrangements in castration-resistant prostate cancer (CRPC). Thus, we sought to examine ERG protein expression in a cohort of rapid autopsy patients with lethal metastatic CRPC (mCRPC).
  
  
  METHODS
  A tissue microarray (TMA) of tumor sites from these patients was evaluated for ERG, prostate-specific antigen (PSA), and androgen receptor (AR) expression by IHC and correlated with ERG rearrangement status by fluorescent in situ hybridization (FISH). IHC was scored as the product of tumor cell staining intensity (0-3) and percentage of cells positive (0-100) (overall product score range = 0-300).
  
  
  RESULTS
  All 16 (100%) ERG rearrangement negative (ERG(neg) ) patients were also negative for ERG tumor cell expression (i.e., IHC product score = 0). Of the 10 ERG rearrangement positive (ERG(pos) ) patients, two (20%) were completely negative for ERG tumor cell expression, while eight (80%) had weak ERG expression (median IHC product score = 5-110). Of these eight ERG(pos) patients, five (63%) had at least one tumor site without any detectable ERG expression. For a given ERG(pos) patient, ERG expression varied both between and within tumor sites; AR and PSA expression also varied between tumor sites, and there was no significant correlation between ERG and AR or PSA expression.
  
  
  CONCLUSIONS
  These data reveal frequent discordance between ERG IHC and ERG FISH in ERG(pos) patients from this unique cohort of heavily treated lethal mCRPC.
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Udager
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Ajjai
authors.initials: A
authors.lastname: Alva
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
mesh_terms: D001344:Autopsy; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D008297:Male; D017430:Prostate-Specific Antigen / Q000235:genetics; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000473:pathology* / Q000556:secondary; D011944:Receptors, Androgen / Q000235:genetics; D046888:Tissue Array Analysis / Q000379:methods; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D011944:Receptors, Androgen; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: TMPRSS2-ERG; androgen receptor (AR); fluorescent in situ hybridization (FISH); immunohistochemistry (IHC); rapid autopsy