title: Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer.
abstract: OBJECTIVE
  The epidermal growth factor receptor (EGFR) is a protein involved in the tumor progression of many cancer types and is an important therapeutic target. To determine its role in prostate cancer, we analyzed 2,497 prostate cancers on the DNA and protein level.
  
  
  METHODS
  Tissue samples from each tumor were brought into a tissue microarray and analyzed by immunohistochemistry and fluorescence in situ hybridization. A subset of cancers was also sequenced for EGFR exon 18 to 21 mutations.
  
  
  RESULTS
  Detectable EGFR expression was found in 18% of cancers and was significantly associated with high grade, advanced stage, and high risk for prostate-specific antigen recurrence in univariate analysis (P < 0.0001, each). Fluorescence in situ hybridization analysis with a dual-labeling probe for centromere 7 and EGFR showed increased EGFR copy number in 3.3% of cases. EGFR copy number gains were mostly due to an overrepresentation of the entire chromosome and were associated with EGFR protein expression (P < 0.0001), high grade (P < 0.0001), and advanced stage (P = 0.0056). Only one cancer had a high-level amplification (>20 EGFR gene copies per cell). This amplification was heterogeneous, involving only approximately 30% of the cancer volume. EGFR mutations were not found in 35 of the cases analyzed.
  
  
  CONCLUSIONS
  Increased EGFR expression is often seen in prostate cancer and is associated with poor prognosis. The significant association of EGFR copy number gains with protein expression argues for the significant role of minimal gene copy number changes for protein expression. Although EGFR expression was not an independent prognostic variable, the potential utility of anti-EGFR medications might be worth further investigation in EGFR-expressing prostate cancer.
authors.affiliation: Martini-Clinic, Prostate Cancer Center, Department of Pathology and Urology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany. tschlomm@uke.uni-hamburg.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Patrick
authors.initials: P
authors.lastname: Kirstein
authors.forename: Liv
authors.initials: L
authors.lastname: Iwers
authors.forename: Birte
authors.initials: B
authors.lastname: Daniel
authors.forename: Thomas
authors.initials: T
authors.lastname: Steuber
authors.forename: Jochen
authors.initials: J
authors.lastname: Walz
authors.forename: Felix H K
authors.initials: FH
authors.lastname: Chun
authors.forename: Alexander
authors.initials: A
authors.lastname: Haese
authors.forename: Jens
authors.initials: J
authors.lastname: Kollermann
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
mesh_terms: D000368:Aged; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation
chemical_list: D004273:DNA, Neoplasm; D066246:ErbB Receptors