Role of urinary cathepsin B and L in the detection of bladder urothelial cell carcinoma.
OBJECTIVE
We tested the hypothesis that urinary cathepsin B and L are associated with bladder cancer recurrence and invasiveness in patients with a history of nonmuscle invasive urothelial carcinoma of the bladder.


METHODS
Cathepsin B and L, and NMP22 were determined in the urine specimens of 188 consecutive subjects with a history of treated urothelial carcinoma of the bladder, 31 with noncancerous urological conditions and 10 healthy subjects. Cathepsin B and L were analyzed as continuous and categorical variables based on their quartile distribution.


RESULTS
Urinary cathepsin L was higher in the 122 patients with cystoscopic evidence of bladder tumor compared with levels in 107 with normal cystoscopy (median 5.9, IQR 4.4 vs 3.0, IQR 3.2, p <0.001). Higher levels of cathepsin L were associated with positive cytology assay results, higher NMP22 and T1 or greater pathological stage (each p <0.001). Area under the ROC curves of NMP22 and cathepsin L for bladder cancer detection were 0.704 (95% CI 0.637-0.772) and 0.793 (95% CI 0.736-0.850), respectively. On multivariate analysis cathepsin L, NMP22 and cytology were associated with invasive pathological stage (OR 1.29, 2.42 and 2.76, respectively, p </=0.002). Urinary cathepsin B was not associated with any outcome variables.


CONCLUSIONS
Urinary cathepsin L is an independent predictor of bladder cancer presence and invasiveness in patients with a history of urothelial carcinoma of the bladder. Further evaluation of this marker is necessary before its use as an adjunct to cystoscopy for urothelial carcinoma of the bladder.
Svatek
Robert S
RS
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Karam
Jose
J
Karakiewicz
Pierre I
PI
Gallina
Andrea
A
Casella
Roberto
R
Roehrborn
Claus G
CG
Shariat
Shahrokh F
SF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002277:Carcinoma / Q000473:pathology / Q000652:urine*; D016022:Case-Control Studies; D002401:Cathepsin B / Q000652:urine*; D056668:Cathepsin L; D002403:Cathepsins / Q000652:urine*; D003546:Cysteine Endopeptidases / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000652:urine*; D019459:Urothelium
D014408:Biomarkers, Tumor; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L