Association of plasma urokinase-type plasminogen activator and its receptor with clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder.
OBJECTIVE
The urokinase plasminogen activation (uPA) system plays an important role in tumor invasion and metastasis by mediating proteolysis, adhesion, and migration of tumor cells. We tested the hypothesis that preoperative plasma levels of uPA and its specific receptor, uPAR, would predict cancer stage and prognosis in patients with transitional cell carcinoma of the bladder.


METHODS
The study group consisted of 51 patients who underwent radical cystectomy for muscle-invasive cancer or Tis, Ta, or T1 transitional cell carcinoma refractory to intravesical therapy and 44 men without cancer. Preoperative plasma levels of uPA and uPAR were measured by enzyme-linked immunosorbent assay in patients with available samples (51 and 38, respectively) and correlated with the clinical and pathologic characteristics and clinical outcome.


RESULTS
Plasma uPA and uPAR levels were both greater in those with bladder cancer than in the healthy subjects (P <0.001). Plasma uPAR levels were greatest in patients with metastases to distant lymph nodes (P = 0.042). Preoperative uPA was independently associated with metastases to regional lymph nodes (P = 0.017), lymphovascular invasion (P = 0.019), disease progression (P = 0.030), and death from bladder cancer (P = 0.038). uPAR was not associated with bladder cancer outcome.


CONCLUSIONS
Plasma uPA and uPAR levels were greater in those with bladder cancer compared with healthy controls. For patients with bladder cancer, a greater preoperative plasma uPA level was an independent predictor of poor outcome after radical cystectomy.
Shariat
Shahrokh F
SF
Scott Department of Urology, Baylor College of Medicine and Methodist Hospital, Houston, Texas 77030, USA.
Monoski
Mara A
MA
Andrews
Ben
B
Wheeler
Thomas M
TM
Lerner
Seth P
SP
Slawin
Kevin M
KM
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002295:Carcinoma, Transitional Cell / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D015653:Cystectomy / Q000379:methods / Q000706:statistics & numerical data; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging / Q000379:methods / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator; D012044:Regression Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood*
D014408:Biomarkers, Tumor; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator