Low circulating levels of ProMMP-2 are associated with adverse prognosis in bladder cancer.

In this study the serum levels of proMMP-2, active MMP-2, TIMP-2 and MMP-2:TIMP2 complex were evaluated. We also studied the correlation of these parameters with clinicopathological parameters in patients suffering from bladder carcinoma and outcome in this patient group. The levels of circulating proMMP-2, active MMP-2, proMMP-9, TIMP-1, TIMP-2 and MMP-2:TIMP-2 complex of 84 patients with bladder cancer were measured by ELISA. The proMMP-2 and TIMP-2 immunoreactive proteins were studied. These results were compared to clinicopathological parameters and patient outcome. Low circulating proMMP-2 levels significantly correlated with poor prognosis. The 5-year disease-specific survival rate was 46% in patients with high levels of proMMP-2 versus 23% in patients with low proMMP-2 levels (p = 0.011). Low TIMP-2 levels could also present as a marker of poor prognosis. In this study, the 5-year disease-specific survival in patients with low circulating TIMP-2 levels was 19% compared to 66% in patients with high TIMP-2 levels (p = 0.004). These results indicate that high levels of circulating proMMP-2 and TIMP-2 levels are both associated with a better clinical course; moreover, total proMMP-2 is an independent prognostic marker of bladder cancer progression.