Expression of three extracellular matrix degradative enzymes in bladder cancer

The relationship between expression of extracellular matrix degradative enz ymes, angiogenesis and survival of multistage bladder cancer was determined . Expression of 3 extracellular matrix degradative enzymes (metalloproteina se-2, -9 and heparanase) and microvessel formation were examined in 40 rese cted bladder cancer specimens by immunohistostochemic staining, and then th e association of the enzyme expression with angiogenesis and various stages of cancer was investigated. Heparanase protein expression in muscular inva sive or lymphnode metastatic cancer was significantly higher than in superf icial or nonmetastatic cancer, respectively (69% vs. 8%, p < 0.001, and 80% vs. 40%, p = 0.028, respectively). Interestingly, heparanase was expressed at much higher levels than matrix metalloproteinase-2 and -9. The mean mic rovessel count in cancers with heparanase expression was significantly high er than that in cancers without heparanase expression (32.3 +/- 18.2 vs. 5. 5 +/- 6.1, p = 0.0008). The microvessel formation was not associated with t he expression of matrix metalloproteinase-2 and -9. The cancer-specific and overall survival rates of patients with heparanase expression were signifi cantly lower than those of patients without it (p = 0.0001 and p = 0.0008, respectively). Multivariate analysis showed that heparanase expression was a significantly independent prognostic factor for both cancer-specific (p = 0.0047) and overall survival (p = 0.0200). Our study suggested that hepara nase plays important roles in invasion, angiogenesis and metastasis of blad der cancer, and thus, this molecule could be a new molecule to inhibit inva sion, angiogenesis and metastasis of bladder cancer. Moreover, our results indicate that expression of heparanase could be a new prognostic factor of this disease. (C) 2001 Wiley-Liss, Inc.