title: Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer.
abstract: OBJECTIVE
  The HER2 oncogene is involved in the biology of many different tumor types and serves as a prognostic marker and a therapeutic target in breast cancer. In contrast to breast cancer, studies on Her2 overexpression and gene amplification in prostate cancer have yielded different results. The purpose of this study was to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in prostate cancer.
  
  
  METHODS
  A tissue microarray containing >2,000 prostate cancers with follow-up data was used. Tissue microarray sections were analyzed on protein and DNA level using two different antibodies (HercepTest, DAKO; Novocastra NCL-CB11) and fluorescence in situ hybridization.
  
  
  RESULTS
  Immunohistochemical analyses showed highly similar results for both antibodies. Detectable Her2 immunostaining was observed in 17.2% for the HercepTest and in 22.5% for the Novocastra antibody with the vast majority of cases showing 1+ or 2+ staining. For both antibodies (HercepTest/Novocastra), significant associations were found between positive staining and high Gleason grade (P < 0.0001, both), advanced pT stage (P < 0.0001/P = 0.0015), rapid tumor cell proliferation (P = 0.0004/P = 0.0071), and tumor recurrence (P < 0.0001, both). HER2 amplification was only found in 1 of 2,525 analyzable cases (0.04%).
  
  
  CONCLUSIONS
  Low-level Her2 overexpression occurs at relevant frequency in prostate cancer and in the absence of gene amplification. Increased Her2 expression may potentially lead to an aggressive behavior of tumor cells through the stimulation of tumor cell proliferation because Her2 staining was shown to be significantly associated with Ki67 labeling index. These data argue for reconsidering anti-Her2 therapy, possibly with modified approaches.
authors.affiliation: Institute of Pathology, Department of Urology, Prostate Cancer Center University Medical Center, Hamburg-Eppendorf, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Birte
authors.initials: B
authors.lastname: Jessen
authors.forename: Lars
authors.initials: L
authors.lastname: Stiedenroth
authors.forename: Eike
authors.initials: E
authors.lastname: Burandt
authors.forename: Jens
authors.initials: J
authors.lastname: Köllermann
authors.forename: Martina
authors.initials: M
authors.lastname: Mirlacher
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
authors.forename: Christian
authors.initials: C
authors.lastname: Eichelberg
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.forename: Tim Henrik
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Thomas
authors.initials: T
authors.lastname: Steuber
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: Thorsten
authors.initials: T
authors.lastname: Schlomm
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases