Expression of vascular endothelial growth factor and its receptors in the anaplastic progression of astrocytoma, oligodendroglioma, and ependymoma
Expression of vascular endothelial growth factor and its receptors in the anaplastic progression of astrocytoma, oligodendroglioma, and ependymoma
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DOI：
10.1097/00000478-199807000-00004
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发表时间：
1998-07-01
影响因子：
5.6
通讯作者：
Chung, LP
中科院分区：
文献类型：
--
作者：
Chan, ASY;Leung, SY;Chung, LP
血管内皮生长因子（VEGF）是一种缺氧诱导的血管生成因子，已知其在大多数多形性胶质母细胞瘤（GBM）病例中上调。VEGF及其受体在室管膜瘤、少突胶质细胞瘤中的表达，特别是在这三种类型胶质细胞瘤的间变性进展中的表达尚未被广泛研究。采用原位杂交（ISH）和逆转录聚合酶链反应（RT-PCR）检测了五十六例胶质瘤中VEGF及其受体的表达，其中室管膜瘤10例，少突胶质细胞瘤12例，间变性少突胶质细胞瘤3例，星形细胞瘤II级6例，间变性星形细胞瘤5例，多形性胶质母细胞瘤20例。结果显示，VEGF在10例室管膜瘤中的8例中表达，在所有间变性少突胶质细胞瘤和多形性胶质母细胞瘤中表达。这些肿瘤显示出相似程度的广泛坏死和血管增生，在坏死区域周围的肿瘤细胞中始终可见VEGF表达。VEGF的表达，虽然目前在较低的水平，也显示在4的12少突胶质细胞瘤，在3的6星形细胞瘤II级，在2的5间变性星形细胞瘤，与区域，而不是弥漫性的阳性结果模式。原位杂交研究的结果与表达指数相关，通过逆转录聚合酶链反应测定。VEGF表达与血管增生（p < 10 - 5）和坏死（p < 10-5）以及微血管密度（p = 0.002，r（s）= 0.41）显著相关。VEGF受体，激酶域区（KDR）和Fms样酪氨酸激酶（Flt-1），也上调肿瘤血管的胶质母细胞瘤多形性，间变性少突胶质细胞瘤，室管膜瘤坏死，而星形细胞瘤II级，间变性星形细胞瘤，少突胶质细胞瘤肿瘤往往表达一个弱到不可检测的信号。所有三种类型的胶质瘤的间变性进展预示着小区域的VEGF表达细胞和早期血管增殖的发生，随后是与坏死区域周围的VEGF诱导和肿瘤血管系统中VEGF受体的表达密切相关的血管生成加速期。
Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic factor, which is known to be upregulated in most cases of glioblastoma multiforme (GBM). The expression of VEGF and its receptors in ependymomas, oligodendrogliomas, and particularly the expression during anaplastic progression of these three types of gliomas has not been studied extensively. Fifty-six gliomas, consisting of 10 ependymomas, 12 oligodendrogliomas, 3 anaplastic oligodendrogliomas, 6 astrocytomas grade II, 5 anaplastic astrocytomas, and 20 glioblastoma multiformes, were investigated for VEGF and receptor expression using in situ hybridization (ISH) and reverse transcription polymerase chain reaction (RT-PCR). Results showed that VEGF was moderately to strongly expressed in 8 of 10 ependymomas and in all anaplastic oligodendrogliomas and glioblastoma multiforme cases. These tumors displayed similar degrees of extensive necrosis and vascular proliferation, with VEGF expression consistently seen in tumor cells around necrotic areas. The VEGF expression, although present at a lower level, also was shown in 4 of 12 oligodendrogliomas, in 3 of 6 astrocytomas grade II, and in 2 of 5 anaplastic astrocytomas, with a regional rather than diffuse pattern of positive result. The findings from the in situ hybridization study correlated with the expression index, as determined by reverse transcription polymerase chain reaction. Expression of VEGF was correlated significantly with vascular proliferation (p < 10(-5)) and necrosis (p < 10-5), as well as with microvessel density (p = 0.002, r(s) = 0.41). The VEGF receptors, kinase domain region (KDR) and Fms-like-tyrosine kinase (Flt-1), also were upregulated in the tumor vasculature of glioblastoma multiforme, anaplastic oligodendrogliomas, and ependymomas with necrosis; whereas the astrocytomas grade II, anaplastic astrocytomas, and oligodendroglioma tumors tended to express a weak to nondetectable signal. Anaplastic progression in all three types of gliomas is heralded by the occurrence of small zones of VEGF-expressing cells and early vascular proliferation, followed by an accelerated phase of angiogenesis closely associated with VEGF induction around areas of necrosis and with the expression of VEGF receptors in the tumor vasculature.