Significance of matrix metalloproteinases and tissue inhibitors of metalloproteinase expression in the recurrence of superficial transitional cell carcinoma of the bladder

Purpose: We determined whether expression levels of matrix metalloproteinase (MMP)-2, MMP-9, membrane-type MMP-1 (MT1-MMP), tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 messenger (m) RNA in superficial transitional cell carcinoma of the bladder may be used as predictors of tumor recurrence. Materials and Methods: Total RNA was extracted from 51 superficial transitional cell carcinomas of the bladder, and expression levels of MMP-2, MMP-9, MT1-MMP, TIMP-1 and TIMP-2 messenger mRNA in these specimens were measured by Northern blot analysis. Results were evaluated in regard to tumor recurrence. Results: Mean MMP-9 and TIMP-2 mRNA expression in the tumors of patients with recurrence were 2.5 and 3-fold higher, respectively, than in these of patients without recurrence despite no significant differences in MMP-2, MT1-MMP or TIMP-1 expression. The recurrence-free survival rate of patients with elevated MMP-9 and TIMP-2 mRNA expression was significantly lower than that of patients with normal MMP-9 and TIMP-2 expression, respectively. In addition, Cox's multivariate analysis revealed that elevated MMP-9 and TIMP-8 were strongly associated with a high incidence of intravesical recurrence of superficial bladder cancer. Conclusions: These results indicate that MMP-9 and TIMP-8 are strongly expressed in the tumors of patients with recurrence compared with those without recurrence and elevated MMP-9 and TIMP-2 may be used as predictors of recurrence in patients with superficial transitional cell carcinoma.