Expression of metalloproteinase-2, metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in transitional cell carcinoma of upper urinary tract: correlation with tumor stage and survival.

摘要

OBJECTIVES: To investigate the relationship between the expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 and pT stage or survival in patients with transitional cell carcinoma of the upper urinary tract. MMP-2 and MMP-9 are associated with tumor invasion in several malignancies. TIMPs exert an anti-invasive effect by blocking MMP activity. Recent studies have shown, however, that TIMPs can also stimulate cell proliferation and angiogenesis. METHODS: Tumor sections surgically removed from 91 patients were examined for expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 by immunohistochemistry. We also determined the proliferation index and microvessel density in each tumor and investigated the independent roles of these factors in tumor stage and survival using multivariate analysis. RESULTS: Of 91 tissue samples, 50, 51, 45, and 39 were positive for MMP-2, MMP-9, TIMP-1, and TIMP-2 expression, respectively. Tumors positive for MMP-2, MMP-9, and TIMP-1 exhibited a greater proliferation index than tumors with negative expression (P <0.001, P = 0.013, and P <0.001, respectively). The microvessel density of tumors positive for MMP-2 and TIMP-1 was greater than that of negative tumors (P <0.001). The expression of MMP-2, MMP-9, and TIMP-1 was an independent predictor of high pT stage. Cox proportional hazard analysis identified TIMP-1 expression as an independent factor for cause-specific survival (odds ratio 5.2, P = 0.011), similar to microvessel density, pT4, and lymph node metastasis. CONCLUSIONS: TIMP-1 expression correlated with pT stage and was an independent predictor of cause-specific survival. Our results suggest that TIMP-1 expression is a potentially useful tool for the selection of postoperative observation strategies in patients with transitional cell carcinoma of the upper urinary tract.