THE EFFECTS OF TUMOR ACTIVITY ON URINARY CONCENTRATION OF MATRIX METALLOPROTEINASES 2 AND 9 IN BLADDER CANCER

Daniltchenko D., Gerhards S., Jung K., Koenig F., Valdman A., Al-Shukri S., Loening S.A.

In cancer cells the increased expression of matrix metalloproteinases (MMPs) leading to tumor invasion and metastases is recorded. The aim of the study was to estimate the diagnostic value of MMP-2 and MMP-9 levels in urine in relation to bladder cancer staging. Urine samples from 130 bladder cancer patients have been studied. The group of patients with transitional cell carcinoma (TCC) (n = 71) consisted of 43 patients with superficial (Ta, T1) and 28 patients with invasive cancer (T2, T3, T4). Among them, there were 38 patients with highly and moderately differentiated tumors (G1, G2) and 33 patients with poorly differentiated bladder carcinoma (G3). The group of patients with inflammatory processes in the bladder consisted of 14 subjects. 45 subjects were recruited for the control group. Detection of MMP-2 and MMP-9 was done by zymography with gelatine. The results were related to creatinine levels in urine. The upper cutoff limit in the control group was 277 mg/g creatinine for MMP-2 and 648 mg/g creatinine for MMP-9. In the bladder cancer group the elevated levels of MMP-2 and MMP-9 were revealed compared with the control group (p < 0.001). In the group of patients with inflammatory processes in the bladder only MMP-9 elevation was detected in comparison with controls (p < 0.01). The levels of MMP-2 and MMP-9 were significantly increased in invasive cancer compared to controls and patients with superficial bladder cancer. In addition, the elevation of MMP-2 and MMP-9 was found in poorly differentiated bladder (G3) cancer compared with the control group (p < 0.001). The sensitivity of zymography in bladder cancer corresponded to 51 and 31% for MMP-2 and MMP-9, respectively. Our results suggest that the levels of MMP-2 and MMP-9 in urine correlate with tumor activity. Therefore, the determination of MMP-2 and MMP-9 levels in urine may have practical importance for diagnosis and evaluation of the progression of bladder cancer.

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