Preoperative plasma HER2 and epidermal growth factor receptor for staging and prognostication in patients with clinically localized prostate cancer.
OBJECTIVE
Human epidermal growth factor receptor-2 (HER2) and epidermal growth factor receptor (EGFR) expression have been associated with disease progression in patients with prostate cancer. We tested the hypothesis that plasma levels of HER2 and/or EGFR are associated with prostate cancer stage and prognosis in patients with clinically localized disease.


METHODS
We measured preoperative plasma HER2 and EGFR levels using commercially available ELISAs on banked plasma from 227 patients treated with radical prostatectomy and bilateral lymphadenectomy for clinically localized prostate adenocarcinoma.


RESULTS
Median preoperative plasma EGFR and HER2 levels were 31.4 ng/mL (interquartile range, 19.2 ng/mL) and 10.0 ng/mL (interquartile range, 2.7 ng/mL), respectively. HER2 was elevated in patients with seminal vesicle invasion (P = 0.033). In separate multivariate analyses that adjusted for the effects of standard preoperative predictors, lower EGFR, higher HER2, and higher HER2/EGFR ratio were associated with prostate-specific antigen (PSA) progression (P = 0.003, P < 0.001, and P < 0.001, respectively). In separate multivariate analyses that adjusted for the effects of standard postoperative predictors, lower EGFR and higher HER2/EGFR ratio were associated with PSA progression (P = 0.027 and P < 0.001, respectively). Among the patients who experienced PSA progression, HER2 was significantly higher (P = 0.023) and EGFR was lower (P = 0.04) in those with features of aggressive disease (i.e., development of metastasis, PSA doubling time <10 months, and/or failure to respond to local salvage radiation therapy).


CONCLUSIONS
Preoperative plasma HER2 and EGFR were associated with prostate cancer progression after radical prostatectomy. Plasma HER2 and EGFR may provide a tool for predicting long-term recurrence-free survival and early metastasis.
Shariat
Shahrokh F
SF
Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9110, USA. Shahrokh.Shariat@UTSouthwestern.edu
Bensalah
Karim
K
Karam
Jose A
JA
Roehrborn
Claus G
CG
Gallina
Andrea
A
Lotan
Yair
Y
Slawin
Kevin M
KM
Karakiewicz
Pierre I
PI
D000328:Adult; D000368:Aged; D018450:Disease Progression; D066246:ErbB Receptors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D016019:Survival Analysis
D066246:ErbB Receptors; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases