Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression in bladder cancer.

Abstract

Matrix metalloproteinase-2 (MMP-2), which degrades the extracellular matrix or the basement membrane, has an essential role in tumor invasion and metastasis. To evaluate the roles of MMP-2, its inhibitor (tissue inhibitor of metalloproteinase-2 [TIMP-2]), and its activator (membrane-type matrix metalloproteinase-1 [MT1-MMP]) in tumor invasion or as a prognostic factor in patients with bladder carcinoma, the authors investigated the expression of MMP-2, TIMP-2, and MT1-MMP in patients with bladder carcinoma. Tissues obtained from 41 patients with bladder carcinoma were used for analysis. Expression of MMP-2, TIMP-2, MT1-MMP, and glyceraldehyde-3-phosphate dehydrogenase was examined by reverse transcriptase-polymerase chain reaction analysis. Correlations between the levels of MMP-2, TIMP-2, and MT1-MMP expression and histologic findings or patient outcome were evaluated. Expression of MMP-2 and TIMP-2 was significantly higher in muscle invasive pT2< or = 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 associated 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 invasive pT2< or = tumor group, patients with a high expression of any of these three genes had a worse prognosis than those with low expression (MMP-2: P < 0.05; TIMP-2: P < 0.05; and MT1-MMP: P = 0.0641). 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 indicators in patients with bladder carcinoma and may be helpful in designing treatment protocols.