Hypoxia-inducible factor 1α/vascular endothelial growth factor axis in astrocytomas.: Associations with microvessel morphometry, proliferation and prognosis
Hypoxia-inducible factor 1α/vascular endothelial growth factor axis in astrocytomas.: Associations with microvessel morphometry, proliferation and prognosis
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DOI：
10.1111/j.1365-2990.2003.00535.x
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发表时间：
2004-06-01
影响因子：
5
通讯作者：
Sakkas, D
中科院分区：
文献类型：
--
作者：
Korkolopoulou, P;Patsouris, E;Sakkas, D
缺氧诱导因子（HIF）-1 α是一种促进缺血驱动的血管生成的转录因子。本研究的目的是在大量弥漫性星形细胞瘤中确定HIF-1 α与血管内皮生长因子（VEGF;脑肿瘤中重要的血管生成分子）、p53表达、血管生成、增殖潜力和临床结果的关系。采用免疫组织化学方法检测83例成人幕上弥漫性星形细胞瘤患者HIF-1 α、VEGF、Ki-67（一种增殖相关标志物）和p53的表达。通过抗CD 34免疫组化突出显示的微血管，用计算机辅助图像分析计数。虽然HIF-1 α和VEGF在大多数病例中表达，但其水平随着级别和增殖潜力的增加而显著增加。HIF-1 α与微血管计数呈正相关，VEGF与总血管面积和圆形血管切片的存在呈正相关。星形细胞瘤和间变性星形细胞瘤中VEGF和p53的表达呈正相关。在单变量分析中，VEGF和HIF-1 α均与整个队列的生存期缩短相关，但当II/III级和IV级分别分析时，其意义就失去了。多因素分析显示，HIF-1 α与分级的结合是一个有意义的预后指标。HIF-1 α表达可用于改善弥漫性星形细胞瘤患者的分级预后信息。它的不良预后作用很可能是由缺氧介导的，缺氧是HIF-1 α积累的驱动力。
Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that promotes ischaemia-driven angiogenesis. The aim of this study was to determine the relation of HIF-1alpha to vascular endothelial growth factor (VEGF; an important angiogenic molecule in brain tumours), p53 expression, angiogenesis, proliferative potential and clinical outcome in a large series of diffuse astrocytomas. Expression of HIF-1alpha, VEGF, Ki-67 (a proliferation-associated marker) and p53 was determined immunohistochemically in 83 adult patients with supratentorial diffuse astrocytomas. Microvessels, highlighted by means of anti-CD34 immunohistochemistry, were enumerated with computer-assisted image analysis. Although HIF-1alpha and VEGF were expressed in the majority of cases, their levels increased significantly with increasing grade and proliferative potential. HIF-1alpha positively correlated with microvessel counts and VEGF with total vascular area and the presence of rounder vessel sections. There was a positive correlation of VEGF with p53 expression in astrocytomas and anaplastic astrocytomas. In univariate analysis, both VEGF and HIF-1alpha were associated with shortened survival in the entire cohort, but lost significance when grades II/III and grade IV were analysed separately. Multivariate analysis revealed that the combination of HIF-1alpha with grade was a significant prognostic indicator. HIF-1alpha expression may be used to refine the prognostic information provided by grade in patients with diffuse astrocytomas. Its adverse prognostic effect is most likely mediated by hypoxia, the driving force for HIF-1alpha accumulation.