Matrix metalloproteinase-2 immunoreactive protein as a prognostic marker in bladder cancer

Objectives. To analyze the expression of matrix metalloproteinase-2 (MMP-2) in bladder cancer specimens and evaluate its value as a prognostic biomarker. MMPs, particularly MMP-2, play an important role in tumor cell invasion and metastasis in several human cancers. Methods. The MMP-2 protein was assayed semiquantitatively in 54 primary bladder carcinomas of varying grade and stage. A specific monoclonal antibody for MMP-2 was used to detect the antigen by a semiquantitative immunohistochemical staining of paraffin-embedded tissue sections. Results. Of the 54 specimens, 35 (65%) overexpressed MMP-2 protein when stained sections were scored independently by three observers. A consensus score was established before clinical data analysis. The 5-year disease-specific survival was significantly (P = 0.0335) lower in the MMP-2 positive cases (n = 35) than in the MMP-2 negative cases (n = 19), 53% versus 77%. The 5 and 10-year relapse-free survival rate was 32% and 24% in the MMP-2 positive patients, respectively, compared with 68% for the MMP-2 negative patients (P = 0.0718). MMP-2 overexpression correlated with bladder cancer stage but not with grade, partly contrary to previous observations. Conclusions. The results of this study demonstrated that MMP-2 protein overexpression may be an independent prognostic biomarker for bladder cancer progression. (C) 2003 Elsevier Inc.