低氧诱导因子-1ɑ、血管内皮生长因子及其受体在胰腺癌中的表达和预后

Expression of hypoxia-inducible factor-1ɑ, vascular endothelial growth factor and its receptors in pancreatic cancer and prognosis of patients

目的探讨胰腺癌组织中低氧诱导因子-1ɑ(HIF-1ɑ)、血管内皮生长因子(VEGF)及VEGF受体1(VEGFR1)、受体2(VEGFR2)对胰腺癌微血管密度(MVD)的影响,以及这些蛋白的表达与胰腺癌根治性手术后患者生存期的关系。方法收集2008年1月—2012年5月在上海交通大学医学院附属仁济医院普外科行胰十二指肠切除术的50例胰腺癌患者的胰腺癌组织病理标本,并随机取其中15例患者的胰腺阴性切缘组织作为对照。采用免疫组织化学法检测胰腺癌组织、阴性切缘组织中HIF-1ɑ、VEGF、VEGFR1、VEGFR2的表达水平。以CD34单克隆抗体显示肿瘤微血管内皮细胞,计算肿瘤内MVD。结果共随访45例,随访率为90%。胰腺癌组织中HIF-1α、VEGF、VEGFR1、VEGFR2阳性率分别为82.0%、84.0%、80.0%和84.0%,均显著高于阴性切缘组织的46.7%、26.7%、0、13.3%(P值均<0.05)。胰腺癌组织中,HIF-1α与VEGF(r=0.564)、VEGFR1(r=0.301)、VEGFR2(r=0.310)、MVD(r=0.443)呈正相关(P值均<0.05),VEGF与VEGFR1(r=0.383)、VEGFR2(r=0.342)呈正相关(P值均<0.05),VEGFR1与VEGFR2呈正相关(r=0.851,P<0.05)。胰腺癌组织中,VEGF(r=0.836)、VEGFR1(r=0.339)、VEGFR2(r=0.284)与肿瘤MVD均呈正相关(P值均<0.05)。结论胰腺癌组织中HIF-1α影响肿瘤分化,能促进VEGF、VEGFR1、VEGFR2表达,诱导肿瘤新生血管形成,增加MVD,促进肿瘤生长,影响患者术后的生存期。

Objective To explore the effect of the expression of hypoxia-inducible factor-1α （HIF-1α）, vascular endothelial growth factor （VEGF）, vascular endothelial growth factor receptor （VEGFR）-1 and VEGFR2 on microvascular density （MVD） in pancreatic cancer, and to analyze the correlation between the expression of these proteins and the prognosis of patients with radical surgery. Methods Fifty paraffin-embedded specimens of pancreatic cancer were collected from the patients who underwent radical pancreatoduodenectomy between January 2008 and May 2012. Fifteen specimens of microscopically negative margin tissue were collected from these patients as control. The expression of HIF-1α, VEGF, VEGFR1 and VEGFR2 were detected by immunohistochemistry. MVD was determined by anti-CD34 monoclonal antibody. Results Totally 45 patients were followed up and the follow-up rate was 90%. The expression of HIF-1α, VEGF, VEGFR1 and VEGFR2 in tumor specimens was 82.0%, 84.0%, 80.0% and 84.0%, respectively, which was significantly higher than the control （P〈0.05）. MVD in tumor specimens was also significantly higher than the control （P〈0.01）. In the tumor specimens, the expression of HIF--1α was positively correlated with VEGF, VEGFR1, VEGFR2 and MVD （r = 0. 564, 0.301, 0.310, and 0. 443, P〈0.05） VEGF was positively correlated with VEGFR1 and VEGFR2 （r = 0. 383 and 0. 342, P〈0. 05） MVD was positively correlated with VEGF, VEGFR1 and VEGFR2 （r = 0. 836, 0.339, and 0. 284, P〈0. 05）. Conclusion HIF-1α may impact the differentiation of pancreatic cancer and activate the expression of VEGF, VEGFR1 and VEGFR2, which induce the neovascularization and the increased MVD and cause poor prognosis.