Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer.
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.
Minner
Sarah
S
Institute of Pathology, Department of Urology, Prostate Cancer Center University Medical Center, Hamburg-Eppendorf, Germany.
Jessen
Birte
B
Stiedenroth
Lars
L
Burandt
Eike
E
Köllermann
Jens
J
Mirlacher
Martina
M
Erbersdobler
Andreas
A
Eichelberg
Christian
C
Fisch
Margit
M
Brümmendorf
Tim Henrik
TH
Bokemeyer
Carsten
C
Simon
Ronald
R
Steuber
Thomas
T
Graefen
Markus
M
Huland
Hartwig
H
Sauter
Guido
G
Schlomm
Thorsten
T
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
D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases