膜型基质金属蛋白酶-1在浸润性肝细胞癌组织的表达及其意义

目的 探讨在浸润性肝细胞肝癌(HCC)中,膜型基质金属蛋白酶-1(MT1-MMP)的表达和意义.方法 随机选取2004年1月至2006年12月间根治性手术切除的HCC标本123例,通过对肿瘤的个数、包膜是否完整、门静脉有无癌栓、有无肝外转移等标准的划分,将其分为浸润转移组(74)及无浸润组(49).术前所有病例均采用酶联免疫吸附试验(ELISA)测定血清血管内皮生长因子(VEGF)水平；并通过免疫组织化学法(ABC),测定两组术后标本癌组织的MT1-MMP蛋白及肿瘤微血管密度(MVD)的表达；定量聚合酶链反应(PCR)测定癌组织MT1-MMP mRNA的表达.结果 浸润组术前血清VEGF:(1 33.89±68.56) μg/L；无浸润组:(100.64±81.37) μg/L,差异有统计学意义(P＜0.01).MT1-MMP主要定位表达在肝癌细胞的胞膜和间质.在浸润组中,MT1-MMP蛋白及mRNA表达量明显高于无浸润组(P＜0.05)；浸润组MVD:11.24±1.49,无浸润组:8.11±2.51,两者比较浸润组MVD的形成量明显增多(P＜0.01).结论 在浸润性肝细胞肝癌中,MT1-MMP的表达明显增高,并伴随血清VEGF的表达上调、癌组织内新生肿瘤微血管的形成增多.MT1-MMP高表达可作为浸润性肝癌的判定指标,并提示临床预后较差.

Expression of membrane type-1 matrix metalioproteinase in invasive hepatocellular carcinoma

Objective To investigate effect and expression of membrane type-1 matrix metalloproteinase ( MT1 -MMP,MMP-14) in invasive hepatocellular carcinoma (HCC).Methods We selected 123 patients with HCC randomly from January 2004 to December 2006 which underwent radical hepatectomy,they were divided into the invasion group (n =74) and the non invasion group (n =49) by the standards including tumor size,number,complete capsule,portal vein thrombosis and extrahepatic metastasis.The serum vascular endothelial growth factor (VEGF) was measured with the quantitative sandwich enzymelinked immunosorbent assay (ELISA) three days before operation.With three-step immunohistochemical technique ( ABC),to determine protein expression of MT1-MMP and microvessel density (MVD) in postoperative tissue samples in the two groups,and mRNA expression of MT1-MMP was measured by quantitative real-time polymerase chain reaction (PCR).Results The preoperative serum VEGF in the invasion group (133.89 ± 68.56 ) μg/L was significantly elevated as compared to that in non invasion group ( 100.64 ± 81.37 ) μg/L ( P ＜ 0.01 ).Tissue location of MT1 -MMP was mainly at membrane and in cytoplasm of HCC cells.In invasive HCC,mRNA and protein expression of MT1-MMP were significantly increased compared to that in no invasive HCC (P ＜ 0.05 ),and MVD expression increased accordingly (P＜0.01).Conclusion In invasive HCC,expression of MT1-MMP was significantly increased,and companied with increased secretion of VEGF,also the formation of tumor angiogenesis in HCC increased.High expression of MT1-MMP in postoperative tissue samples could be used as a valuable predictor for invasive HCC,and it prompted poor clinical prognosis.