肝细胞癌中血管内皮生长因子和cNOS与血管生成及细胞增殖的关系

目的　观察血管内皮生长因子 (VEGF)及含激酶插入区受体 (KDR)在原发性肝癌中的表达情况及其与cNOS表达的相关性 ,探讨它们在肝癌肿瘤性血管生成、肿瘤细胞增殖和转移过程中的作用。　方法　收集手术切除的 80例原发性肝癌、4 0例肝硬化、2 0例正常肝组织标本 ,应用免疫组织化学和原位杂交的方法观察VEGF及其KDR、cNOS在肝细胞癌中的表达情况 ,分析VEGF及其受体KDR、cNOS与微血管密度 (MVD)、肿瘤细胞增殖指数和转移的关系。　结果　肝癌组织中癌细胞VEGF的表达与MVD、细胞增殖指数明显相关 (P <0 0 1和P <0 0 5 ) ,与肝癌内皮细胞中cNOSmRNA的表达之间也有相关性 (Pearson列联系数 =0 2 984 ,P <0 0 5 )。内皮细胞中cNOSmRNA与VEGF均阳性者微血管密度、细胞增殖指数均明显高于cNOSmRNA阴性和VEGF阳性者 (P <0 0 1) ,也明显高于两者均阴性者 (P <0 0 1)。　结论　肝细胞癌中癌细胞VEGF的表达与血管生成、细胞增殖和肝癌转移密切相关 ,且内皮细胞cNOSmRNA的表达可能参与VEGF的促血管生成作用。

RELATIONSHIPS BETWEEN EXPRESSION OF VEGF,cNOS AND ANGIOGENESIS,CELL PROLIFERATION IN HUMAN HEPATOCELLULAR CARCINOMA

Objective To investigate the relationships between the expression of VEGF,its receptor KDR/flk-1,cNOS mRNA and angiogenesis,cell proliferation,metastasis in human hepatocellular carcinoma(HCC). Methods Immunohistochemical analysis using antibodies against VEGF and its kinase insert domain receptor (KDR) was carried out.cNOS mRNA expression in HCC,liver cirrhosis and normal liver tissue was observed by in situ hybridization.CD34 immunostaining was used to measure the microvascular density(MVD)and proliferative index was evaluated by Ki-67 immunostaining. Results The expressions of VEGF and KDR of HCC were significantly related to MVD,proliferation and metastasis of HCC(P<0.01,<0.05,<0.01,respectively).A significant positive relationship between the expression of cNOS mRNA in endothelial cells and the expression of VEGF in tumor cells was observed(Pearson=0.2984,P<0.05).The MVD in HCC with positive expression of both cNOS mRNA and VEGF was the highest,but cNOS mRNA had no effect on MVD in HCC where the VEGF was negative.Conclusion The result suggested that the expession of VEGF in HCC was significantly related to angiogenesis,cell proliferation and metastasis of HCC,and cNOS might be involved in VEGF signaling required for angiogenesis of HCC.