Imbalance between serum matrix metalloproteinase-2 and its inhibitor as a predictor of recurrence of urothelial cancer

Abstract

Serum levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) were evaluated as prognostic indicators of the recurrence of urothelial cancer. Sera were obtained from 127 healthy control subjects and 97 urothelial cancer patients who underwent complete resection and were measured for MMP-2 and TIMP-2 using a one-step enzyme immunoassay. The relationship between the serum MMP-2/TIMP-2 ratio and the recurrence of urothelial cancer was examined. The mean serum MMP-2/TIMP-2 ratio in the 31 advanced urothelial cancer patients with recurrence was significantly higher than that in the 22 patients without recurrence (P = 0.0029) and in the 44 superficial bladder cancer patients (P < 0.0001). The 1- and 3-year disease-free survival rates in the patients with high MMP-2/TIMP-2 ratios (50% and 12%) were significantly poorer than those of the patients with normal ratios (82% and 56%) (P = 0.0152). Univariate and multivariate analyses of recurrence demonstrated that the serum MMP-2/TIMP-2 ratio is a significant independent indicator of advanced urothelial cancer. Our results indicate that an imbalance between the serum levels of MMP-2 and TIMP-2 could be a new predictor of recurrence in advanced urothelial cancer patients.