缺氧诱导因子-1α表达与胰腺癌病理学特征及新生血管生成的关系

The relation between the expression of hypoxia-inducible factor-1 alpha and angiogenesis in human pancreatic cancer

目的 研究胰腺癌组织中缺氧诱导因子 - 1α(HIF- 1α)的表达与胰腺癌病理学特征的关系 ,以及 HIF- 1α表达与血管内皮生长因子 (VEGF)和肿瘤微血管密度 (MVD)之间的相互关系。方法 应用免疫组织化学方法检测 4 7例胰腺癌和 10例正常胰腺组织中 HIF- 1α和 VEGF蛋白的表达。同时用CD34单克隆抗体标记胰腺癌和正常胰腺组织中的微血管。结果 HIF- 1α和 VEGF蛋白在 4 7例胰腺癌组织中的阳性表达率分别为 5 5 .3% (2 6 / 4 7)和 6 1.7% (2 9/ 4 7) ,而在 10例正常胰腺组织中均未见表达。胰腺癌组织 MVD为 37.6 1± 14 .3,正常胰腺组织为 7.5 5 ± 2 .4 ,二者间有显著性差别 (t'=13.5 1,P<0 .0 0 1)。 HIF- 1α和 VEGF蛋白阳性表达率及 MVD均与胰腺癌的浸润和转移密切相关 (χ2 =4 .32 ,6 .0 1,4 .75 ,4 .6 2 ;t=2 .38,3.92 ;P<0 .0 5 ) ,而与胰腺肿块大小、组织学分级和患者术后 1年生存率无关 (P>0 .0 5 )。HIF- 1α与 VEGF(r=0 .32 9,χ2 =5 .71;P<0 .0 5 )、HIF- 1α与 MVD(r=0 .5 94 ,t=4 .96 ;P<0 .0 0 1)及 VEGF与 MVD(r=0 .36 6 ,t=2 .6 4 ;P<0 .0 5 )间在胰腺癌组织中的表达均呈显著的正相关性。结论 在缺氧状态下 ,胰腺癌组织中 HTF- 1α基因被激活 ,过量表达 HIF- 1α蛋白 ,并通过诱导 VEGF?

Objective To study the relation between expression of hypoxia-inducible factor-1 alpha (HIF-1α) and pathological characteristics in human pancreatic cancer and its relation with vascular endothelial growth factor (VEGF) and microvessel density (MVD). Method Immunohistochemistry staining (PicTure TM two steps method) was used to detect expression of HIF-1α, VEGF and CD34 in 47 paraffin-embeded pancreatic carcinomas and 10 normal pancreases tissues, and MVD was calculated on the sections marked with CD34 antibody. Results In pancreatic carcinoma, the positive rates of HIF-1α and VEGF and the level of MVD were significantly higher than those in normal pancreases tissues (55.3% vs 0; 61.7% vs 0; 37.61 ± 14.32 vs 7.55 ± 2.42, respectively; P=0.001, 0.0003; t'=13.51; P < 0.01). HIF-1α and VEGF proteins expression and MVD were closely correlated with invasion and lymph node or distant metastasis (χ2=4.32,6.01,4.75,4.62,t=2.38,3.92,P < 0.05), rather with size, histological grade and 1-year survival rate of patients (P > 0.05). There was a positive relationship between the expression of HIF-1α and VEGF and MVD level (r=0.329, 0.594, 0.366; χ2=5.71,t=4.96, 2.64; P < 0.05). Conclusions The HIF-1α gene may be activated by hypoxia, and the over expression of HIF-1α protein may induce tumor angiogenesis by activating the transcription of VEGF gene, promoting invasion and metastasis of pancreatic cancer. The expression level of HIF-1α, VEGF and MVD may be a useful biological index judging metastasis of pancreatic cancer.