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颅内脑膜瘤中的血管生成:免疫组织化学和分子研究

Angiogenesis in intracranial meningiomas: immunohistochemical and molecular study.

作者信息

Pistolesi S, Boldrini L, Gisfredi S, De Ieso K, Camacci T, Caniglia M, Lupi G, Leocata P, Basolo F, Pingitore R, Parenti G, Fontanini G

机构信息

Department of Surgery, University of Pisa, Italy.

出版信息

Neuropathol Appl Neurobiol. 2004 Apr;30(2):118-25. doi: 10.1046/j.0305-1846.2003.00516.x.

DOI:10.1046/j.0305-1846.2003.00516.x
PMID:15043709
Abstract

Much of the morbidity of intracranial meningiomas is related to the degree of tumour vascularity and the extent of peritumoural vasogenic oedema. Several studies have shown that vascular endothelial growth factor (VEGF) is up-regulated in meningiomas, although its relationship with tumour vasculature is still unclear. In order to better understand the angiogenic assessment of intracranial meningiomas, we analysed its vascular pattern, both as number and as morphologic configuration of microvessels. Moreover, we investigated the mRNA-VEGF expression, relating this expression to vascular pattern. A total of 40 intracranial meningiomas, classified as benign (31 cases), atypical (7 cases), and anaplastic (2 cases) were analysed. RT-PCR analyses of mRNA-VEGF and competitive-PCR were performed. VEGF expression and microvessel density (MVD) were also immunohistochemically investigated. Grade II-III meningiomas showed numerous small microvessels (mean: 34), while the majority of Grade I showed few larger vessels (mean: 13.09) (P = 0.000003). A microvessel pattern overlapping into atypical subtype was found in eignt of the 31 (25.8%) Grade I meningiomas. A significant association was found between grading and vascular pattern (P = 0.0002), as well as between the MVD and the immunohistochemical expression of VEGF (P = 0.0005). The expression of mRNA agreed with the immunohistochemical expression of the protein (P < 0.0001). A total of 39 cases expressed the 121 VEGF isoform and, among these, 28 cases also expressed the 165 isoform. Only 9 cases expressed both isoforms 165 and 189. Grade II and III meningiomas showed a preponderant expression of soluble isoforms (121 and 165). These results prompt us to speculate that the microvessel pattern could underlie a higher metabolic demand, probably due to a rapid growth with a consequent worse clinical behaviour of the tumour. In this sense, the vascular pattern may be used as a prognostic factor, in order to mostly focus attention on those Grade I meningiomas which have a higher likelihood of either recurrence or development of perilesional oedema. The pattern of vasculature itself seems to be dependent on the types of VEGF isoforms: the Grade II-III meningiomas (that presented numerous microvessels) expressed the soluble isoforms 121 and 165, while the isoform 189 was more frequently detected in Grade I meningiomas.

摘要

颅内脑膜瘤的许多发病率与肿瘤血管化程度和瘤周血管源性水肿的范围有关。多项研究表明,血管内皮生长因子(VEGF)在脑膜瘤中上调,但其与肿瘤血管系统的关系仍不清楚。为了更好地理解颅内脑膜瘤的血管生成评估,我们分析了其血管模式,包括微血管的数量和形态结构。此外,我们研究了mRNA-VEGF表达,并将其与血管模式相关联。共分析了40例颅内脑膜瘤,分为良性(31例)、非典型(7例)和间变性(2例)。进行了mRNA-VEGF的RT-PCR分析和竞争性PCR。还通过免疫组织化学研究了VEGF表达和微血管密度(MVD)。II-III级脑膜瘤显示有许多小微血管(平均:34个),而大多数I级脑膜瘤显示较少的较大血管(平均:13.09个)(P = 0.000003)。在31例I级脑膜瘤中有8例(25.8%)发现微血管模式与非典型亚型重叠。分级与血管模式之间(P = 0.0002)以及MVD与VEGF的免疫组织化学表达之间(P = 0.0005)均发现有显著相关性。mRNA表达与蛋白质的免疫组织化学表达一致(P < 0.0001)。共有39例表达VEGF 121异构体,其中28例还表达165异构体。只有9例同时表达165和189异构体。II级和III级脑膜瘤显示可溶性异构体(121和165)的优势表达。这些结果促使我们推测,微血管模式可能是更高代谢需求的基础,可能是由于肿瘤快速生长导致临床行为更差。从这个意义上说,血管模式可作为一个预后因素,以便主要关注那些复发或发生病灶周围水肿可能性更高的I级脑膜瘤。血管系统本身的模式似乎取决于VEGF异构体的类型:II-III级脑膜瘤(有许多微血管)表达可溶性异构体121和165,而I级脑膜瘤中更频繁检测到异构体189。

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