MMP-2和TIMP-2在肝癌中的表达及其意义

The significance of matrix metalIoproteinase-2 and tissue inhibitor of matrix metalIoproteinase-2 expression in human hepatocellular carcinoma

目的:探讨基质金属蛋白酶-2（MMP-2）及其组织抑制剂（TIMP-2）在人肝癌组织中的表达和肝癌生物学行为之间的关系。方法:应用免疫组织化学ABC法研究了56例人肝癌组织中MMP-2和TIMP-2的表达。结果:肝癌组织中MMP-2蛋白表达阳性率为55.4％（31/56）,较癌旁肝组织阳性率89.3％（50/56）明显减低（P<0.01）。包膜完整组肝癌MMP-2表达阳性率为78.6％,包膜突破组60％,无包膜组40.7％,包膜完整组与无包膜组相比有显著性差异（P<0.05）。TIMP-2在肝癌组织和癌旁肝组织中的表达阳性率分别为37.5％（21/56）和66.1％（37/56）,肝癌中的表达比癌旁肝组织表达也明显降低（P<0.05）。包膜完整组肝癌TIMP-2表达阳性率为64.3％,包膜突破组为46.7％,无包膜组为18.5％,包膜完整组与无包膜组相比有显著性差异（P<0.05）。经统计学分析表明,肝癌组织中MMP-2表达与TIMP-2表达有显著相关性（P<0.05）。结论:肝癌包膜形成是抑制肿瘤浸润侵袭的重要防御反应;TIMP-2可能是通过抑制包膜的降解发挥阻遏肿瘤转移扩散的作用;降解包膜胶原成分的MMP-2及其组织抑制剂TIMP-2在癌组织中的表达状态对于判断肝癌的浸润侵袭程度有重要价值。

Objective: To evaluate the significance of matrix metalloproteinase-2 ( MMP-2 ) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) expression in human hepatocellular carcinoma (HCC) and the relationship betwwen two proteins. Methods: The expression of MMP-2 and TIMP-2 were observed in 56 cases human HCC using immunohistochemistry technique. Results; The positive rate of MMP-2 protein expression was 55.4% (21/56) in HCC, and was markedly decreased than in paratumor samples (89.3%, 50/56) (P<0.01) . The positive rate of MMP-2 protein expression in HCC, which had fibrous encasulation, incomplete encapsulation and no encapsulation, was 78.6%, 60% and 40.7% respectively. The expression rate of MMP-2 in tumors without encapsulation was significantly lower than in tumors with fibrous encapsulation( P<0.05). The positive rate of TIMP-2 protein expression in tumors and paratumor samples was 37.5% (21/56) and 66.1 % (37/56) respectively. The expression levels of TIMP-2 in HCC were significantly reduced when compared with paratumor samples. (P<0.05) The positive rate of TIMP-2 protein expression in HCC, which had fibrous encapsulation, incomplete encapsulation and no encapsulation, was 64.3%, 46.7% arid 18.5% respectively. The expression rate of TIMP-2 in tumors without encapsulation was significantly lower than that in tumors with fibrous encapsulation (P<0.05). There was a significant correlation between the expressions of MMP-2 and TIMP-2 proteins in HCC( P<0.05). Conclusion .The formation of tumor encapsulation is the main limitative reaction of tumor infiltration and invasion. It is probably that TImp-2 protein may play an important role to inhibit the disruption of fibrous encapsulation. The balanced expression of MMP-2 and TIMP-2 proteins in HCC is a significant index to predict tumor invasion and metastasis.