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 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< 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).


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.
Kanayama
H
H
Department of Urology, School of Medicine, The University of Tokushima, Kuramoto, Japan.
Yokota
K
K
Kurokawa
Y
Y
Murakami
Y
Y
Nishitani
M
M
Kagawa
S
S
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D014158:Transcription, Genetic; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
D000970:Antineoplastic Agents; D019716:Tissue Inhibitor of Metalloproteinase-2; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2