Excretion of matrix metalloproteinases 2 and 9 in urine is associated witha high stage and grade of bladder carcinoma

Objectives. To analyze the excretion of matrix metalloproteinases (MMPs) 2 and 9 in the urine of patients with bladder cancer according to the stage a nd grade of tumor and to evaluate their diagnostic clinical validity. In nu merous 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 mali gnancy, 14 patients with cystitis, and 43 patients with Stage Ta-T1, 18 pat ients 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 w as performed by univariate statistical analysis, logistic regression analys is, and receiver operating characteristic analysis. Results, The upper cutoff limit for MMP-2 and MMP-9 excretion was 277 mug/g creatinine and 648 mug/g creatinine, respectively. Levels of MMP-2 and MMP -9 correlated with each other and with tumor stage and grade. Elevated excr etions were mainly observed in patients with invasive tumors (Stage T2-T4). In the receiver operating characteristic analysis, the areas under the cur ves for MMP-2 and MMP-9 were significantly higher in patients with muscle-i nvasive than in patients with noninvasive tumors. Related to the cutoff lim its, the overall sensitivity to detect bladder cancer was 0.51 for MMP-2 an d 0.31 for MMP-9. In logistic regression analysis, MMP-2 showed the best re sults. 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 tum or progression and recurrence in the future. UROLOGY 57: 675-679, 2001. (C) 2001, Elsevier Science Inc.