[Relationship of expression unbalance of matrix metalloproteinase and tissue inhibitor of metalloproteinase to invasiveness and metastasis in gastric carcinomas]

Abstract

Background & objective: Matrix metalloproteinase-9 (MMPs) and its tissue inhibitor of metalloproteinase-1 (TIMPs) have the important regulatory roles in the processes during tumor invasion and metastasis. Observing the coexpression of matrix metalloproteinase 9(MMP-9) and tissue inhibitor of metalloproteinase 1(TIMP-1) in gastric carcinomas, this study was designed to investigate the relationship of the expression unbalance of MMP-9 and TIMP-1 to the invasiveness, metastasis, and prognosis in gastric carcinomas.

Methods: By using immunohistochemistry, the expression of MMP-9, TIMP-1, and proliferating cell nuclear antigen Ki-67 was detected in 256 gastric cancers, and the patients were followed-up.

Results: The expressive degree of MMP-9 in the tumor invasion beyond musculariis propria(70.13%) was higher than that within lamina propria or submucosa(42.50%, P < 0.05) and its expression in tumor was positively associated with tumor cell proliferation index and lymph node metastasis, and its expression in high TNM stage(75.00%) was higher than those in low TNM stage(46.15%, P < 0.05). The relation of the expression of TIMP-1 to the depth of invasion, lymph node metastasis, and TNM stage was negative(Pearson contingency coefficient were 0.1688, 0.3556, and 0.3004, respectively P < 0.05). There were four groups of the unbalance expression of MMP-9 and TIMP-1 in gastric carcinomas. While the frequency of the serosa invasion and lymph node metastasis in the group of the expression of MMP-9 over TIMP-1 was significantly higher than those in the groups of the expression of TIMP-1 over MMP-9 or the balance expression of MMP-9 and TIMP-1. However, prognosis of the patients with the expression of MMP-9 over TIMP-1 was significantly worse than that with expression of TIMP-1 over MMP-9(P < 0.05).

Conclusion: The expression of MMP-9 was positively related to the tumor invasiveness and metastasis in gastric cancers, however the association between the positive expression of TIMP-1 and the invasiveness and metastasis was negative. The relationship of MMP-9 and TIMP-1 to the invasiveness and metastasis in gastric carcinomas was that MMP-9 promotes and TIMP-1 inhibits tumor metastasis. The patients with MMP-9 positive expression and TIMP-1 negative expression are poorer prognosis.