This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Durkan, G. C. Articles by Mellon, J. K. Search for Related Content PubMed PubMed Citation Articles by Durkan, G. C. Articles by Mellon, J. K.

Prognostic Significance of Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 in Voided Urine Samples from Patients with Transitional Cell Carcinoma of the Bladder¹

Department of Surgery [G. C. D., P. H. R., D. E. N., J. K. M.] and Cancer Research Unit [G. C. D., J. E. N., J. L.], The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom

Purpose: To study the role of urinary matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in bladder cancer and their relationship to tumor progression.

Experimental design: MMP-1 and TIMP-1 were measured by ELISA in urine samples from 131 patients with bladder tumors (7 cis, 74 Ta, 29 T1, and 21 T2-T4; 46 G₁, 41 G₂, and 37 G₃), 5 patients with prostate cancer, 33 patients with benign lower urinary tract disorders, and 36 healthy volunteers. Complete clinical data were available for 100 patients with bladder cancer with a median follow-up time of 24 months (range: 4–39 months).

Results: MMP-1 was detected in urine samples from 21 of 131 (16%) patients with bladder cancer but was undetectable in samples from all other groups (P < 0.0001). Urinary MMP-1 was detected in a higher percentage of patients with T2-T4 tumors and G₃ tumors than patients with cis/Ta/T1 or G₁-G₂ tumors (P = 0.04 and P = 0.0074, respectively). Patients with detectable concentrations of urinary MMP-1 had higher rates of disease progression (P = 0.04) and death from bladder cancer (P = 0.02) than patients with undetectable urinary MMP-1. All patient groups had higher urinary TIMP-1 concentrations than healthy volunteers (P = 0.02). Patients with muscle-invasive tumors had higher concentrations of urinary TIMP-1 than patients with cis/Ta/T1 tumors (P = 0.037), but there was no association between TIMP-1 and tumor grade. Urinary TIMP-1 levels strongly correlated with tumor size (P = 0.0002). Progression-free survival rates were lower for patients with urinary TIMP-1 concentrations above the median (1.8 ng/ml, P = 0.04), but urinary TIMP-1 levels were not related to disease-specific survival. Patients with T2-T4 tumors and G₃ tumors had significantly lower urinary MMP-1:TIMP-1 ratios than patients with Ta/T1 bladder tumors (P = 0.039) or G₁-G₂ tumors (P = 0.0415).

Conclusions: Where urinary MMP-1 is detectable, the patient is more likely to have a bladder tumor of advanced stage or grade and may be at increased risk of disease progression and death of bladder cancer. The relationship between urinary TIMP-1, muscle-invasion, and disease progression in bladder cancer is at variance with its role as an inhibitor of MMPs and warrants additional evaluation.

This article has been cited by other articles:

				R. Roy, G. Louis, K. R. Loughlin, D. Wiederschain, S. M. Kilroy, C. C. Lamb, D. Zurakowski, and M. A. Moses Tumor-Specific Urinary Matrix Metalloproteinase Fingerprinting: Identification of High Molecular Weight Urinary Matrix Metalloproteinase Species Clin. Cancer Res., October 15, 2008; 14(20): 6610 - 6617. [Abstract] [Full Text] [PDF]

				S. E. Pories, D. Zurakowski, R. Roy, C. C. Lamb, S. Raza, A. Exarhopoulos, R. G. Scheib, S. Schumer, C. Lenahan, V. Borges, et al. Urinary Metalloproteinases: Noninvasive Biomarkers for Breast Cancer Risk Assessment Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1034 - 1042. [Abstract] [Full Text] [PDF]

				S. Singh, U. P. Singh, J. K. Stiles, W. E. Grizzle, and J. W. Lillard Jr. Expression and Functional Role of CCR9 in Prostate Cancer Cell Migration and Invasion Clin. Cancer Res., December 15, 2004; 10(24): 8743 - 8750. [Abstract] [Full Text] [PDF]

				R. C. K. Jordan, M. Macabeo-Ong, C. H. Shiboski, N. Dekker, D. G. Ginzinger, D. T. W. Wong, and B. L. Schmidt Overexpression of Matrix Metalloproteinase-1 and -9 mRNA Is Associated with Progression of Oral Dysplasia to Cancer Clin. Cancer Res., October 1, 2004; 10(19): 6460 - 6465. [Abstract] [Full Text] [PDF]

				G. C. Durkan, J. E. Nutt, C. Marsh, P. H. Rajjayabun, M. C. Robinson, D. E. Neal, J. Lunec, and J. K. Mellon Alteration in Urinary Matrix Metalloproteinase-9 to Tissue Inhibitor of Metalloproteinase-1 Ratio Predicts Recurrence in Nonmuscle-invasive Bladder Cancer Clin. Cancer Res., July 1, 2003; 9(7): 2576 - 2582. [Abstract] [Full Text] [PDF]