Expression of three extracellular matrix degradative enzymes in bladder cancer

The relationship between expression of extracellular matrix degradative enzymes, angiogenesis and survival of multistage bladder cancer was determined. Expression of 3 extracellular matrix degradative enzymes (metalloproteinase‐2, ‐9 and heparanase) and microvessel formation were examined in 40 rese...

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Published in:International journal of cancer 2001-09, Vol.95 (5), p.295-301
Main Authors: Gohji, Kazuo, Hirano, Hiroshi, Okamoto, Masayuki, Kitazawa, Sohei, Toyoshima, Minako, Dong, Jian, Katsuoka, Yoji, Nakajima, Motowo
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
angiogenesis
Biological and medical sciences
bladder cancer
extent
extracellular matrix degradative enzyme
Female
Glucuronidase - biosynthesis
Humans
Male
Matrix Metalloproteinase 2 - biosynthesis
Matrix Metalloproteinase 9 - biosynthesis
Medical sciences
Middle Aged
Multivariate Analysis
Neoplasm Staging
Neovascularization, Pathologic - enzymology
Nephrology. Urinary tract diseases
Prognosis
survival
Survival Rate
Tumors of the urinary system
Urinary Bladder Neoplasms - blood supply
Urinary Bladder Neoplasms - enzymology
Urinary Bladder Neoplasms - pathology
Urinary tract. Prostate gland
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Summary:The relationship between expression of extracellular matrix degradative enzymes, angiogenesis and survival of multistage bladder cancer was determined. Expression of 3 extracellular matrix degradative enzymes (metalloproteinase‐2, ‐9 and heparanase) and microvessel formation were examined in 40 resected bladder cancer specimens by immunohistostochemic staining, and then the association of the enzyme expression with angiogenesis and various stages of cancer was investigated. Heparanase protein expression in muscular invasive or lymph‐node metastatic cancer was significantly higher than in superficial 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 microvessel count in cancers with heparanase expression was significantly higher 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 the expression of matrix metalloproteinase‐2 and ‐9. The cancer‐specific and overall survival rates of patients with heparanase expression were significantly 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 heparanase plays important roles in invasion, angiogenesis and metastasis of bladder cancer, and thus, this molecule could be a new molecule to inhibit invasion, angiogenesis and metastasis of bladder cancer. Moreover, our results indicate that expression of heparanase could be a new prognostic factor of this disease. © 2001 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/1097-0215(20010920)95:5<295::AID-IJC1051>3.0.CO;2-A