Increased urokinase-type plasminogen activator receptor and epidermal growth factor receptor in serum of patients with prostate cancer.
OBJECTIVE
Prostate cancer cell motility and invasion have been linked to the up-regulated signaling of epidermal growth factor receptor and urokinase-type plasminogen activator receptor. We analyzed the expression of serum urokinase-type plasminogen activator receptor and epidermal growth factor receptor in the serum of patients with clinical suspicion of prostate cancer to evaluate the possible role as prostate cancer markers.


METHODS
Serum was collected from 79 consecutive patients referred to our institution for transrectal ultrasound guided prostate biopsy. All blood samples were obtained before prostate biopsy. Total urokinase-type plasminogen activator receptor and epidermal growth factor receptor antigen in serum were measured by specific enzyme-linked immunosorbent assays. Gleason score, the number of positive cores, maximum percent of cancer and inflammation were considered on biopsy. Patients determined to have prostate adenocarcinoma underwent radical retropubic prostatectomy. Gleason score, pathological stage (extraprostatic extension), surgical margins, seminal vesicle involvement, perineural infiltration, lymphovascular invasion and cancer volume were evaluated in radical retropubic prostatectomy specimens.


RESULTS
The 30 patients with prostate cancer had significantly higher levels of serum urokinase-type plasminogen activator receptor and epidermal growth factor receptor in comparison to those without prostate cancer but not significantly higher levels of prostate specific antigen. Urokinase-type plasminogen activator receptor and epidermal growth factor receptor levels closely correlated in the serum of patients with prostate cancer. In a multivariate model high serum epidermal growth factor receptor increased the probability of positive biopsies by 1.9 times. ROC analysis revealed that serum epidermal growth factor receptor had 93.3% sensitivity and 98% specificity for detecting prostate cancer at a cutoff of 67.9 ng/ml. Urokinase-type plasminogen activator receptor and epidermal growth factor receptor were significantly higher in patients with extraprostatic extension, seminal vesicle involvement and perineural infiltration in the radical retropubic prostatectomy specimens. Serum urokinase-type plasminogen activator receptor was the only independent predictive serum marker of extraprostatic extension, seminal vesicle involvement and perineural infiltration.


CONCLUSIONS
The measurement of urokinase-type plasminogen activator receptor and epidermal growth factor receptor in the serum of patients with clinical suspicion of prostate cancer might provide clinically relevant information on the state of the prostate gland. Measuring serum epidermal growth factor receptor could help predict which patients have prostate cancer, while serum urokinase-type plasminogen activator receptor over expression seems to be related to tumor extraprostatic spread.
Milanese
Giulio
G
Department of Urology, Laboratory of Cellular and Molecular Biology, School of Medicine, Polytechnic University of the Marche Region, Ancona, Italy.
Dellabella
Marco
M
Fazioli
Francesca
F
Pierpaoli
Elisa
E
Polito
Massimo
M
Siednius
Nicolai
N
Montironi
Rodolfo
R
Blasi
Francesco
F
Muzzonigro
Giovanni
G
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D066246:ErbB Receptors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*
D014408:Biomarkers, Tumor; D055293:Receptors, Urokinase Plasminogen Activator; D066246:ErbB Receptors