Excretion of matrix metalloproteinases 2 and 9 in urine is associated with a high stage and grade of bladder carcinoma.
OBJECTIVE
To analyze the excretion of matrix metalloproteinases (MMPs) 2 and 9 in the urine of patients with bladder cancer according to the stage and grade of tumor and to evaluate their diagnostic clinical validity. In numerous carcinomas, increased expression of MMPs is associated with a higher grade of malignancy and poor prognosis.


METHODS
The study population included 44 controls without evidence of malignancy, 14 patients with cystitis, and 43 patients with Stage Ta-T1, 18 patients with Stage T2, and 10 patients with Stage T3-T4 bladder cancer. MMP-2 and MMP-9 excretion in urine samples was measured with gelatin zymography and related to the urine creatinine concentration. The evaluation of data was performed by univariate statistical analysis, logistic regression analysis, and receiver operating characteristic analysis.


RESULTS
The upper cutoff limit for MMP-2 and MMP-9 excretion was 277 microg/g creatinine and 648 microg/g creatinine, respectively. Levels of MMP-2 and MMP-9 correlated with each other and with tumor stage and grade. Elevated excretions were mainly observed in patients with invasive tumors (Stage T2-T4). In the receiver operating characteristic analysis, the areas under the curves for MMP-2 and MMP-9 were significantly higher in patients with muscle-invasive than in patients with noninvasive tumors. Related to the cutoff limits, the overall sensitivity to detect bladder cancer was 0.51 for MMP-2 and 0.31 for MMP-9. In logistic regression analysis, MMP-2 showed the best results.


CONCLUSIONS
Urinary excretion of MMP-2 and MMP-9 is associated with a high stage and grade of bladder cancer, and they may serve as indicators of tumor progression and recurrence in the future.
Gerhards
S
S
Department of Urology, University Hospital Charité, Humboldt University Berlin, Berlin, Germany.
Jung
K
K
Koenig
F
F
Daniltchenko
D
D
Hauptmann
S
S
Schnorr
D
D
Loening
S A
SA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D003556:Cystitis / Q000175:diagnosis / Q000201:enzymology / Q000652:urine; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000652:urine*; D020780:Matrix Metalloproteinase 9 / Q000652:urine*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000652:urine*
D014408:Biomarkers, Tumor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9