PROGNOSTIC VALUES OF MATRIX METALLOPROTEINASE-2 AND TISSUE INHIBITOR OF METALLOPROTEINASE-2 EXPRESSION IN BLADDER-CANCER

BACKGROUND. Matrix metalloproteinase-2 (MMP-2), which degrades the ext racellular matrix or the basement membrane, has an essential role in t umor invasion and metastasis. To evaluate the roles of MMP-2, its inhi bitor (tissue inhibitor of metalloproteinase-2 [TIMP-2]), and its acti vator (membrane-type matrix metalloproteinase-1 [MT1-MMP]) in tumor in vasion or as a prognostic factor in patients with bladder carcinoma, t he authors investigated the expression of MMP-2, TIMP-2, and MT1-MMP i n patients with bladder carcinoma. METHODS. Tissues obtained from 41 p atients with bladder carcinoma were used for analysis. Expression of M MP-2, TIMP-2, MT1-MMP, and glyceraldehyde-3 phosphate dehydrogenase wa s examined by reverse transcriptase-polymerase chain reaction analysis . Correlations between the levels of MMP-2, TIMP-2, and MT1-MMP expres sion and histologic findings or patient outcome were evaluated. RESULT S. Expression of MMP-2 and TIMP-2 was significantly higher in muscle i nvasive pT2 less than or equal to bladder tumors than in pT1a tumors ( MMP-2: P < 0.0005; TIMP-2: P < 0.005). Moreover, high levels of MMP-2 and TIMP-2, as well as MT1-MMP expression, all were strongly associate d with decreased survival (MMP-2: P < 0.0001; TIMP-2: P < 0.0001; and MT1-MMP: P < 0.005). Even within the radically cystectomized muscle in vasive pT2 less than or equal to tumor group, patients with a high exp ression of any of these three genes had a worse prognosis than those w ith low expression (MMP-2:P < 0.05; TIMP-2: P < 0.05; and MT1-MMP: P = 0.0641). CONCLUSIONS. MMP-2 and TIMP-2 are believed to contribute to the invasive properties of bladder carcinoma. The authors report that expression of MMP-2, TIMP-2, and MT1-MMP are useful prognostic indicat ors in patients with bladder carcinoma and may be helpful in designing treatment protocols. (C) 1998 American Cancer Society.