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 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...

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Published in:Cancer 1998-04, Vol.82 (7), p.1359-1366
Main Authors: Kanayama, Hiro‐omi, Yokota, Kin‐ya, Kurokawa, Yasushi, Murakami, Yoshihide, Nishitani, Masaaki, Kagawa, Susumu
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antineoplastic Agents - metabolism
Biological and medical sciences
bladder cancer
Carcinoma - diagnosis
Carcinoma - metabolism
Carcinoma - mortality
Carcinoma - pathology
Female
Gelatinases - metabolism
Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism
Humans
Male
Matrix Metalloproteinase 2
Matrix Metalloproteinases, Membrane-Associated
Medical sciences
Metalloendopeptidases - metabolism
Middle Aged
Multivariate Analysis
Nephrology. Urinary tract diseases
Polymerase Chain Reaction
Prognosis
prognostic factor
reverse transcriptase‐polymerase chain reaction
Survival Rate
Tissue Inhibitor of Metalloproteinase-2 - metabolism
tissue inhibitor of metalloproteinases‐2
Transcription, Genetic
tumor invasion
Tumors of the urinary system
Urinary Bladder
Urinary Bladder Neoplasms - diagnosis
Urinary Bladder Neoplasms - metabolism
Urinary Bladder Neoplasms - mortality
Urinary Bladder Neoplasms - pathology
Urinary tract. Prostate gland
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Summary:BACKGROUND 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. METHODS 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. RESULTS Expression of MMP‐2 and TIMP‐2 was significantly higher in muscle invasive pT2≤ 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≤ 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). 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 indicators in patients with bladder carcinoma and may be helpful in designing treatment protocols. Cancer 1998;82:1359‐66. © 1998 American Cancer Society. Expression of matrix metalloproteinase‐2 and tissue inhibitor of metalloproteinase‐2 is useful in estimating tumor invasion and may enhance the accuracy of conventional parameters used to determine the prognosis of patients with bladder carcinoma.
ISSN:0008-543X
1097-0142
DOI:10.1002/(SICI)1097-0142(19980401)82:7<1359::AID-CNCR20>3.0.CO;2-4