Ranieri G, Gasparini G
Division of Medical Oncology, Azienda Ospedali Riuniti, Reggio Calabria, Italy.
Methods Mol Med. 2001;57:99-113. doi: 10.1385/1-59259-136-1:99.
Angiogenesis, the formation of new blood vessels from a preexisting vascular network, is a complex multistep process under the control of positive and negative factors (bi1,bi2). Growth, progression, and metastasis of malignant tumors are angiogenesis-dependent processes (3-bi5). There is compelling evidence that development of angiogenic phenotype is a common pathway in the biology of tumor progression and metastasis, and the angiogenesis is correlated with other molecular mechanisms (e.g., the control of wild-type p53 on vascular endothelial growth factor or thrombospondin-1) (6,7). Angiogenesis can be directly determined, and so it may be useful as a biomarker (8-bi10). Tumor microvessel density (11-13) or tissue angiogenic factors expression may predict which patients are at different risk of metastasis (14-16), and serum levels of angiogenic factors may serve as tumor markers (17,18).At present the most widely used method to assess angiogenesis is quantification of intratumoral microvessel density (IMD) of the primary tumor by using specific markers for endothelial cells such as factor VIII-related antigen (FVIII-RA), anti-CD31 (platelet endothelial cell adhesion molecule, PECAM), or anti-CD34 antibodies (19,22), using a standard immunocytochemistry immunoperoxidase technique to stain micro vessels (23,24). The basic principles of immunocytochemistry are described in Chapter 2 by Brooks and use of immunocytochemistry employing antibodies against factor VIII-related antigen and CD31 is described in Chapter 8 by Turner and Harris.
血管生成是指从预先存在的血管网络形成新的血管，是一个受正负因子（bi1，bi2）控制的复杂多步骤过程。恶性肿瘤的生长、进展和转移是依赖血管生成的过程（3-bi5）。有令人信服的证据表明，血管生成表型的发展是肿瘤进展和转移生物学中的一条共同途径，并且血管生成与其他分子机制相关（例如，野生型p53对血管内皮生长因子或血小板反应蛋白-1的控制）（6,7）。血管生成可以直接测定，因此它可能作为一种生物标志物有用（8-bi10）。肿瘤微血管密度（11-13）或组织血管生成因子表达可以预测哪些患者处于不同的转移风险中（14-16），并且血管生成因子的血清水平可以作为肿瘤标志物（17,18）。目前评估血管生成最广泛使用的方法是通过使用内皮细胞特异性标志物如因子VIII相关抗原（FVIII-RA）、抗CD31（血小板内皮细胞黏附分子，PECAM）或抗CD34抗体，对原发性肿瘤的瘤内微血管密度（IMD）进行定量（19,22），使用标准免疫细胞化学免疫过氧化物酶技术对微血管进行染色（23,24）。免疫细胞化学的基本原理在布鲁克斯所著的第2章中进行了描述，而使用针对因子VIII相关抗原和CD31的抗体进行免疫细胞化学的方法在特纳和哈里斯所著的第8章中进行了描述。
