缺氧诱导因子-1α的表达与肝癌血管生成的关系

Relationship between hypoxia-inducible factor-1 alpha expression and angiogenesis in human hepatocellular carcinoma

目的:探讨缺氧诱导因子-1α(HIF-1α)的表达与肝癌血管生成的关系及HIF-1α、血管内皮生长因子(VEGF)、微血管密度(MVD)对肝癌生物学行为的影响。方法:应用免疫组织化学法检测肝癌组织中HIF-1α、VEGF的表达,用CD34单克隆抗体标记肿瘤血管内皮细胞,计数肝癌组织中的肿瘤MVD。结果:肝癌组织中HIF-1α、VEGF的表达阳性率分别为71%、75%,MVD为41.32±9.47,明显高于正常肝组织(P<0.01),HIF-1α与VEGF的表达及MVD的变化呈显著正相关(r=0.37,P<0.05;r=0.685,P<0.001)。HIF-1α、VEGF、MVD与肝癌的淋巴转移、包膜及静脉侵犯密切相关(P<0.05)。结论:HIF-1α的表达与肝癌新生血管的生成密切相关,HIF-1α的过表达、高MVD与肝癌的不良生物学行为有关,影响肝癌的预后,可能成为预测肝癌转移复发的参考指标。

Objective： To investigate the relationship between the expression of hypoxia inducible factor-lalpha （HIF-1α） and angiogenesis in hepatocellular carcinoma （HCC） and to investigate the effects of HIF-1α, vascular endothelial growth factor （VEGF） and microvessel density （MVD） on the biological features of HCC. Methods： HIF-1α,VEGF expression was detected by immunohistochemistry in 48 eases of HCC and 11 cases of normal liver tissue. MVD of the section marked with CD34 antibody was calculated, and the relationship between MVD and the clinical pathological characteristics of HCC was analyzed. Results： The positive rate of HIF-1α and VEGF in HCC was 71% （34/483, 75%（36/48）, and MVD was 41.32 ＋ 9.47, which were significantly higher in HCC tissue than tbose in normal liver tissue （P 〈 0.01 ）. HIF-1α was positively correlated with VEGF and MVD （r = 0.37, P 〈 0.05 .r = 0.685, P 〈 0.001 ）, and the expression of VEGF were tightly correlated with MVD （r = 0.641, P 〈 0.001）. HIF-1α, VEGF and MVD were closely associated with lymph node-metastasis, microscopic venous invasion, and capsule formation. Conclusion： Significant correlation is found between the overexpression of HIF-1α and angiogenesis in HCC. The aggressive behavior of HCC may be due to the overexpression of HIF-1α and abnormal MVD. HIF-1α plays an important role in the prognosis of HCC, and may become useful reference predictor for tumor recurrence or metastasis.