【作者】 吴晓慧； 王顺祥； 李建坤； 彭利； 唐瑞峰； 张萌；

【Author】 Wu Xiao-Hui Wang Shun-Xiang Li Jian-Kun Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei medical university & Hebei provincial tumor hospital, Shijiazhuang, 050011, China

【机构】 河北医科大学第四医院暨河北省肿瘤医院肝胆外科；

【摘要】 目的:探讨HIF-1 α、VEGF的蛋白表达与肝细胞癌新生血管生成及侵袭转移特性之间的关系,以及HIF-1 α和VEGF之间的关系,明确HIF—1在肝细胞癌新生血管生成中的作用及机制。方法:选用50例肝细胞癌组织和32例癌旁肝组织标本,12例正常肝组织作正常对照。采用免疫组化S-P法检测肝细胞癌组织、癌旁肝组织标本和正常肝组织中HIF-1 α、VEGF的表达和计数MVD值,并结合患者的临床病理指标进行统计学分析。结果:HIF-1 α在肝细胞癌组织、癌旁肝组织和正常肝组织中的阳性表达率分别为 50．0％(25／50)、16．1％(5／32)、8．3％(1／12),VEGF的阳性表达率分别为80．0％(40／50)、59．4％(19／32)、41．7％(5／12)。肝细胞癌中HIF-1 α和VEGF的表达均显著高于癌旁和正常肝组织(P<0．05),肝细胞癌组织MVD值为26．92±11．25,显著高于癌旁(17．08±9．31)和正常肝组织(15．22±6．38)(P<0．05)。 HIF-1 α蛋白表达与患者年龄、性别、肿瘤大小、有无肝内或淋巴结转移及AFP水平等无关(P>0．05),HIF-1 α蛋白表达在有门静脉或胆管癌栓组显著高于无门静脉或胆管癌栓组 (P<0．05),肿瘤低分化组显著高于中高分化组(P<0．05)。 VEGF蛋白的表达与患者年龄、性别、肿瘤大小、AFP水平及肿瘤分化程度等无关(P>0．05),VEGF蛋白的表达在有肝内或淋巴结转移组显著高于无肝内或淋巴结转移组(P<0．05), 有门静脉或胆管癌栓组显著高于无门静脉或胆管癌栓组(P <0．05)。肝细胞癌组织中HIF-1 α与VEGF表达有关(P <0．05)。HIF-1 α与VEGF共同表达阳性组的MVD值(30． 71±10．08)显著高于共同表达阴性组MVD值(18．30±4．29) (P<0．05)。结论:HIF-1 α和VEGF与肝细胞癌的发生、发展及侵袭转移的生物学行为有关,HIF—1可能通过调节 VEGF的表达促进肝细胞癌新生血管生成,从而促使肝细胞癌侵袭转移。联合检测HIF-1 α和VEGF的表达对于预测肝细胞癌复发转移、判断预后和制定个体化综合治疗方案有一定的临床价值。更多还原

【Abstract】 Objective: To test the expressions of HIF-1 α, VEGF and counting microvascular density(MVD) in HCCs, paratumor tissues and normal liver tissues and determine the relationship between the former three factors and neoangiogenesis in HCC tissues and the feature of invasion and metastasis, furthermore to document the mechanism of HIF-1 in neoangiogenisis of HCC. Methods: Fifty tumor tissue samples and thirty-two tumor-surrounding tissue samples were obtained from primary HCC patients undergoing surgical resection. Twelve normal liver tissue samples were taken from previously patients with benign tumor. S-P method of Im-munohistochemistry was used to detect the expression of HIF-1 α, VEGF and MVD. Statistical analysis was used to determine the relationship between their expression and clinicopathological parameters. Results: HIF-1 α -positive stain was observed in twenty-five of 50 tumor tissue samples (50.0%), and VEGF-positive stain in forty (80.0%). In contrast, HIF-1 α -positive stain was observed only in 5 of 32 tumor-surrounding tissue samples (16.1%) and VEGF-positive stain in 19 (59.4%). Only 1 of 12 (83%) HIF-1 α -positive stain in normal liver tissue samples was observed and VEGF-positive stain in five (41.7%). Statistical analysis revealed that HIF-1 α -positive and VEGF-positive stain rate were higher in tumor tissue than that in tumor-surrounding tissue and in normal liver tissue (P<0.05). Numerical value of MVD is 26.92 ± 11.25 in tumor tissue samples, 17.08 ± 9.31 in tumor-surrounding tissue samples and 15.22 ± 638 in nor- mal liver tissue samples. Numerical value of MVD was significantly higher in tumor tissue than that in tumor-surrounding tissue and normal liver tissue (P<0.05). The HIF-1 a -positive stain has nothing to do with age, sex, the tumor size, intrahepatic or lymphatic metastasis and AFP (P>0.05), but it is significantly higher in HCC with portal vein or biliary duct tumor thrombosis than that in without (P<0.05). In poorly differentiated HCC HIF-1 α-positive stain expression is significantly higher than that in moderately and well differentiated HCC (P<0.05). VEGF-positive stain was uncorrelated with age, sex, the tumor size, hepatic function, AFP level and the level of tumor differentiation (P>0.05), but it is significantly higher in HCC with intrahepatic or lymphatic metastasis, and portal vein or biliary duct tumor thrombosis than that in without respectively (P<0.05). There was a positive relationship between HIF-1 α-positive expression and VEGF-positive expression in HCCs (P<0.05). In tumor tissue samples with both HIF-1 α-positive and VEGF-positive stain, the value of MVD is 30.71 ± 10.08, but in both HIF-1 α-negative and VEGF-negative stain tissue samples, the value is 18.30 ± 4.29. The value of MVD is higher in the former than that in the latter (P<0.05). Conclusion: HIF-1 α and VEGF are closely correlated with the occurrence, development, invasion and metastasis of HCC. HIF-1 α could ac更多还原