原发性肝癌中结构型一氧化氮合酶mRNA的表达及其意义

Expression and significance of nitric oxide synthase in human hepatocellular carcinoma

目的 观察结构型一氧化氮合酶 (cNOS)在正常肝组织、肝硬化和原发性肝细胞癌 (以下简称肝癌 )中的表达情况 ,探讨其在肝癌的发生、血管生成、肿瘤细胞增殖和转移过程中的作用。方法 运用原位杂交技术检测cNOSmRNA在 2 0例正常肝组织、4 0例肝硬化、80例肝癌标本中的表达分布和定位情况 ;采用S P免疫组化方法测量组织的微血管密度 (MVD)和细胞增殖指数。结果 肝癌及非癌性肝组织中血管内皮细胞、肝癌细胞及单核和 (或 )吞噬细胞上均可见有cNOSmRNA的表达。肝癌中癌细胞cNOSmRNA阳性表达率明显高于肝硬化组织中的肝细胞 (P <0 .0 1) ,而正常肝组织中的肝细胞未见有cNOSmRNA的表达 ,肝癌、肝硬化中内皮细胞cNOSmRNA阳性表达率明显高于正常肝组织 (P <0 .0 1)。肝癌组织中内皮细胞cNOSmRNA阳性表达者的MVD、细胞增殖指数明显高于阴性表达者 (P <0 .0 1,<0 .0 5 )。肝癌中细胞增殖指数随着MVD的增大而增高 (r =0 .35 77,P <0 .0 1) ,且有转移倾向的肝癌MVD和细胞增殖指数明显高于无转移倾向的肝癌 (P <0 .0 1,<0 .0 5 )。单核和 (或 )吞噬细胞中cNOSmRNA表达在正常肝组织、肝硬化及肝癌之中未见明显差别 ,且与肝癌组织学分型、MVD、细胞增殖指数及转移无关。结论 肝癌细胞cNOSmRNA表达可能与肝癌的发生、

Objective To investigate the expression and significance of nitric oxide synthase (cNOS) mRNA in primary hepatocellular carcinoma(HCC), cirrhotic liver and normal liver tissue. Methods cNOS mRNA expression in 80 HCC, 40 cirrhotic liver and 20 normal liver tissue were observed by in situ hybridization. CD34 immunostain was used to measure the microvascular density (MVD) and Ki 67 immunostain to proliferative index. Results Expression of cNOS mRNA was observed in the liver cancer cells, endothelial cells in the non cancerous liver tissues and mononuclear and/or phagocytes. Expression of cNOS mRNA in tumor cells of HCC was higher than that in the liver cells of cirrhotic liver ( P <0.01) which was higher than the normal liver tissue. Expression in the endothelial cells was higher in HCC and cirrhotic liver than those in the normal liver tissue( P <0.01). HCC with positive cNOS mRNA expression in the endothelial cells showed higher extent of neovascularization and degree of proliferative index. The more MVD, the higher proliferative index, which increased in metastatic tumors. Conclusion cNOS mRNA expression was involved in oncogenesis, angiogenesis and progression of hepatocellular carcinoma. [