Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer.
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.
Schlomm
Thorsten
T
Martini-Clinic, Prostate Cancer Center, Department of Pathology and Urology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany. tschlomm@uke.uni-hamburg.de
Kirstein
Patrick
P
Iwers
Liv
L
Daniel
Birte
B
Steuber
Thomas
T
Walz
Jochen
J
Chun
Felix H K
FH
Haese
Alexander
A
Kollermann
Jens
J
Graefen
Markus
M
Huland
Hartwig
H
Sauter
Guido
G
Simon
Ronald
R
Erbersdobler
Andreas
A
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
D004273:DNA, Neoplasm; D066246:ErbB Receptors