Weidner N
Department of Pathology, University of California, San Francisco 94143-0102.
Semin Diagn Pathol. 1993 Nov;10(4):302-13.
The first requirement of a new prognostic indicator is that it should possess a clear biological significance. Indeed, much evidence shows that tumor growth and metastasis depend on neovascularization. Tumor angiogenesis (TA) refers to the growth of new vessels toward and within the tumor; unless tumor neovascularization occurs, cell proliferation reaches a steady state, and the tumor grows no larger than about 2 mm greatest diameter. Moreover, for tumor cells to metastasize, they must gain access to the vasculature from the primary tumor, survive the circulation, localize in the target organ, and induce angiogenesis in that target organ. TA is necessary both at the beginning and at the end of the metastatic cascade of events. Recently, my colleagues and I showed that a statistically significant correlation exists between incidence of metastases and microvessel density (MVD) of primary invasive breast carcinomas. Now, subsequent studies have shown that the association of prognosis with MVD exists not only in breast carcinoma but also in non-small-cell lung carcinoma, prostate carcinoma, and head-and-neck carcinoma. This article reviews the concepts and mechanisms of TA, the evidence supporting its role in growth and metastasis of solid tumors, and how measuring MVD within invasive tumors correlates with factor VIII-related antigen, blood vessel.
一种新的预后指标的首要要求是它应具有明确的生物学意义。的确,大量证据表明肿瘤生长和转移依赖于新血管形成。肿瘤血管生成(TA)是指新血管向肿瘤内部生长;除非发生肿瘤新血管形成,细胞增殖会达到稳定状态,肿瘤最大直径不会超过约2毫米。此外,肿瘤细胞要发生转移,必须从原发肿瘤进入脉管系统,在循环中存活,在靶器官定位,并在该靶器官诱导血管生成。TA在转移事件级联反应的起始和终末阶段都是必需的。最近,我和我的同事表明,原发性浸润性乳腺癌的转移发生率与微血管密度(MVD)之间存在统计学上的显著相关性。现在,后续研究表明,预后与MVD的关联不仅存在于乳腺癌中,也存在于非小细胞肺癌、前列腺癌和头颈癌中。本文综述了TA的概念和机制、支持其在实体瘤生长和转移中作用的证据,以及如何测量浸润性肿瘤内的MVD与血管内皮因子VIII相关抗原、血管的相关性。