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Levels of Matrix Metalloproteases in Bladder Cancer Correlate with Tumor Grade and Invasion

Biological Therapies [B. D., F. B.] and Histopathology [A. H.] Laboratories, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX; Departments of Oncology [J. W., H. W.], Surgery [P. A., G. W.], and Pathology [T. K.], Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 0NN; and Department of Surgery, Freeman Hospital, Newcastle-Upon-Tyne NE7 7DN [D. N., D. T.], United Kingdom

We have used quantitative zymography to measure levels of the type IV collagenases matrix metalloproteinase (MMP)-9 and MMP-2 in 42 biopsies of transitional cell carcinoma and in 7 biopsies of normal bladder. Mean levels of MMP-9 were significantly higher in tumor compared with normal samples (P = 0.08). Levels of MMP-9 and active MMP-2 increased with tumor grade (test for trend, P = 0.002 and P = 0.05, respectively). Levels of MMP-9 and activated MMP-2 were also higher in invasive tumors than in superficial ones (P = 0.001 and P = 0.008, respectively). In situ hybridization studies showed that the mRNAs for both MMP-2 and MMP-9 were located chiefly in the stroma rather than epithelial tumor cells and were concentrated at the interface between the two tissues.

Received 7/22/93. Accepted 10/ 4/93.

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