基质金属蛋白酶和组织金属蛋白酶抑制剂表达失衡与胃癌浸润转移的关系

背景和目的：基质金属蛋白酶－9（matrix metalloproteinase-9,MMP-9)及其相应的组织金属蛋白酶抑制剂－1（tissue inhibifor of metalloproteinase-1 TIMP-1)在肿瘤细胞浸润和转移过程中起重要的调节作用,本研究观察二者在胃癌中的共表达情况,探讨其表达失衡与胃癌浸润转移和预后的关系。方法：应用免疫组化方法检测256例胃癌细胞MMP－9、TIMP－1和细胞增殖核抗原Ki-67的表达,并行回顾性随访。结果：胃癌侵及肌层以上者的MMP－9表达（70．13％）明显高于胃癌仅限于粘膜及粘膜下层者（42．50％,P＜0．05）,MMP－9表达与肿瘤细胞增殖指数、淋巴结转移呈正相关,TNM分期高者MMP－9表达（75．00％）高于TNM分期低者（46．15％,P＜0．05）;TIMP－1的表达与胃癌浸润程度、淋巴结转移及TNM分期呈负相关（Pearson列联系数分别为0．1688,0．3556和0．3004,P＜0．05）。胃癌组织中MMP－9和TIMP－1表达失衡有4种类型,其中MMP－9表达超过TIMP－1者胃癌发生浆膜浸润、淋巴结转移的比例明显高于TIMP－1表达超过MMP－9者或二者表达平衡者（P＜0．05）,而术后胃癌患者的生存率情况则相反,MMP－9表达超过TIMP－1者术后生存率明显低于TIMP－1表达超过MMP－9者（P＜0．05）。结论：MMP－9阳性表达与胃癌浸润转移呈正相关,而TIMP－1阳性表达与胃癌浸润转移呈负相关,二者在胃癌浸润转移中的关系表现为MMP－9促进肿瘤转移为主,TIMP－1对胃癌有独立的抑制作用,MMP－9阳性表达而TIMP－1阴性表达者提示胃癌患者预后不良。

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

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.