title: PTEN loss and ERG protein expression are infrequent in prostatic ductal adenocarcinomas and concurrent acinar carcinomas.
abstract: BACKGROUND
  Prostatic ductal adenocarcinoma is an unusual and aggressive morphologic subtype of prostate cancer. PTEN gene deletion and ERG gene rearrangement are among the most common genomic changes in acinar prostate cancers. Though ductal adenocarcinoma most commonly occurs with synchronous usual-type acinar adenocarcinoma, little is known about the molecular phenotype of these mixed tumors.
  
  
  METHODS
  We used genetically validated immunohistochemistry (IHC) assays to assess PTEN and ERG status in a group of 37 surgically treated ductal adenocarcinomas and 18 synchronous acinar adenocarcinomas where we have previously reported ERG gene rearrangement status by fluorescence in situ hybridization (FISH). A group of 34 stage and grade-matched pure acinar adenocarcinoma cases was studied as a control.
  
  
  RESULTS
  ERG IHC was highly concordant with ERG FISH results, with 100% (36/36) concordance among ductal adenocarcinomas and 91% (31/34) concordance among 34 pure acinar carcinomas. Similar to previous FISH results, ERG expression by IHC was significantly less common among ductal adenocarcinomas (11% or 4/37) and their synchronous acinar tumors (6% or 1/18) compared to matched pure acinar adenocarcinoma cases (50% or 17/34; P = 0.0005 and 0.002, respectively). PTEN loss by IHC was also less common among ductal adenocarcinomas (18% or 6/34) and their synchronous acinar tumors (22% or 4/18) compared to matched pure acinar carcinomas (50% or 17/34; P = 0.01 and 0.08, respectively). As expected, PTEN loss was enriched among ERG positive compared to ERG-negative tumors in the pure acinar tumor control group (2.5-fold enrichment; P = 0.04) however this was not observed among the ductal adenocarcinomas (1.5 fold enrichment; P = NS). Of ductal adenocarcinomas with an evaluable synchronous acinar component, ERG status was concordant in 94% (17/18) and PTEN status was concordant in 94% (16/17).
  
  
  CONCLUSIONS
  Based on PTEN and ERG, ductal adenocarcinomas and their concurrent acinar carcinomas may be clonally related in some cases and show important molecular differences from pure acinar carcinoma.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Morais
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Mehsati
authors.initials: M
authors.lastname: Herawi
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Antoun
authors.initials: A
authors.lastname: Toubaji
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Roula
authors.initials: R
authors.lastname: Albadine
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hicks
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.|Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.|Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.|Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Lotan
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018267:Carcinoma, Acinar Cell / Q000378:metabolism* / Q000473:pathology; D044584:Carcinoma, Ductal / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051059:PTEN Phosphohydrolase / Q000172:deficiency*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis*; D000071230:Transcriptional Regulator ERG
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: ERG; PTEN; ductal adenocarcinoma; endometrioid; immunohistochemistry; prostatic adenocarcinoma