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[血管生成与乳腺肿瘤。病理学家的观点]

[Angiogenesis and breast neoplasms. The pathologist's point of view].

作者信息

Guinebretière J-M

机构信息

Service de pathologie, centre René-Huguenin, 35, rue Dailly, 92210 Saint-Cloud, France.

出版信息

Gynecol Obstet Fertil. 2005 Mar;33(3):140-6. doi: 10.1016/j.gyobfe.2005.03.002.

Abstract

Angiogenesis is an essential step of the tumoral growth and of the metastatic dissemination. It provides the nutriments necessary to the tumor and by the direct contact of the lumen vessels, facilitates its metastatic extension. The activation implies a large number of different agents which closely interact with the extracellular matrix. The intra tumoral vessels constitute an irregular network with numerous shunts. Their wall is also abnormal, incompletely covered by pericytes, and their basal membrane is thin and fragmented, sometimes absent. These features are responsible for an increased permeability and despite the large number of vessels, deserve a less effective oxygenation. The hypoxia induced secondarily activates the synthesis of angiogenic factors. The pathologist receives today help from immunohistochemistry for the evaluation of angiogenesis. This means facilitates the detection of vessels by use of specific antibodies directed against the endothelial cells (CD31, CD34, fVIIIrag...). It also allows the quantification of vessels or "microvascular density". Its importance varies from one patient to another and for different areas of a same tumour, the "hot-spot" generally located at its periphery. Despite its heterogeneity and the complexity of mechanisms involved in the regulation, the microvascular density appears to be an independent prognostic factor for tumour of different histological types. Immunohistochemistry also permits the evaluation of different characteristics of vessels and the tumour such as the activators (VEGF, FGF...) or their specific receptors (VEGF-R). Such analysis is also important for the determination of the prognosis but appears more interesting for the selection of the antiangiogenic treatment. However, this step will require the standardization of the immunohistochemistry techniques and the implementation of an external quality control.

摘要

血管生成是肿瘤生长和转移扩散的关键步骤。它为肿瘤提供必要的营养物质,并通过管腔血管的直接接触,促进肿瘤的转移扩展。这种激活涉及大量不同的因子,它们与细胞外基质密切相互作用。肿瘤内血管构成一个不规则的网络,有许多分流。其管壁也不正常,周细胞覆盖不完全,基底膜薄且破碎,有时甚至缺失。这些特征导致通透性增加,尽管血管数量众多,但氧合效果不佳。继发的缺氧会激活血管生成因子的合成。如今,病理学家可借助免疫组织化学来评估血管生成。这一方法通过使用针对内皮细胞的特异性抗体(CD31、CD34、fVIIIrag等)便于检测血管。它还能对血管进行定量或“微血管密度”测定。其重要性因患者而异,对于同一肿瘤的不同区域,“热点”通常位于肿瘤周边。尽管其具有异质性且调控机制复杂,但微血管密度似乎是不同组织学类型肿瘤的一个独立预后因素。免疫组织化学还可评估血管和肿瘤的不同特征,如激活因子(VEGF、FGF等)或其特异性受体(VEGF-R)。这种分析对判断预后也很重要,但对于选择抗血管生成治疗似乎更有意义。然而,这一步骤需要免疫组织化学技术的标准化以及实施外部质量控制。

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