Fox S B, Gatter K C, Bicknell R, Going J J, Stanton P, Cooke T G, Harris A L
Nuffield Department of Pathology, University of Oxford, John Radcliffe Hospital, United Kingdom.
Cancer Res. 1993 Sep 15;53(18):4161-3.
Current studies of tumor angiogenesis rely on the concept that endothelium proliferates 30-40 times faster in tumors than in normal tissues. This evidence is based on histological autoradiographic data largely from animal studies. To assess endothelial cell proliferation in human cancer we used the more sensitive and specific technique of immunohistochemistry. We measured the frequency and distribution of endothelial cell proliferation and examined their relationship to tumor cell proliferation. For the first time, we also correlated endothelial and tumor cell proliferation with tumor vascularity. Twenty breast carcinomas from patients exposed to bromodeoxyuridine 3-8 h prior to surgery were double immunostained using antibodies to CD31 (as a marker of endothelium) and bromodeoxyuridine (as a marker of proliferation). The labeling index (LI) for both tumor and endothelial cells was determined and tumor vascularity was assessed by counting the number of CD31 positive vessels. Endothelial cell proliferation was predominantly at the tumor periphery while tumor cell proliferation occurred throughout the lesion. The mean LIs for endothelium and tumor were 2.2% (range, 0.8-5.3) and 7.3% (range, 1.3-17.1), respectively. There was no correlation between tumor and endothelial cell LI (P = 0.414) or between the tumor LI or endothelial cell LI and tumor vascularity (P = 0.08 and P = 0.39, respectively). These findings suggest that previous studies in animal tumors have significantly overestimated endothelial cell proliferation and that its importance in tumor angiogenesis may be related more to continual remodeling and migration of vessels than to proliferation alone.
目前对肿瘤血管生成的研究基于这样一个概念，即肿瘤内皮细胞的增殖速度比正常组织快30 - 40倍。这一证据主要基于大量来自动物研究的组织学放射自显影数据。为了评估人类癌症中内皮细胞的增殖情况，我们使用了更敏感和特异的免疫组织化学技术。我们测量了内皮细胞增殖的频率和分布，并研究了它们与肿瘤细胞增殖的关系。我们还首次将内皮细胞和肿瘤细胞的增殖与肿瘤血管生成相关联。对20例在手术前3 - 8小时接触溴脱氧尿苷的乳腺癌患者的肿瘤进行双重免疫染色，使用抗CD31抗体（作为内皮细胞的标志物）和抗溴脱氧尿苷抗体（作为增殖的标志物）。测定肿瘤细胞和内皮细胞的标记指数（LI），并通过计数CD31阳性血管的数量来评估肿瘤血管生成。内皮细胞增殖主要发生在肿瘤周边，而肿瘤细胞增殖则发生在整个病变区域。内皮细胞和肿瘤细胞的平均LI分别为2.2%（范围0.8 - 5.3）和7.3%（范围1.3 - 17.1）。肿瘤细胞和内皮细胞的LI之间无相关性（P = 0.414），肿瘤LI或内皮细胞LI与肿瘤血管生成之间也无相关性（分别为P = 0.08和P = 0.39）。这些发现表明先前在动物肿瘤中的研究显著高估了内皮细胞的增殖，并且其在肿瘤血管生成中的重要性可能更多地与血管的持续重塑和迁移有关，而不仅仅是增殖。
