Vermeulen P B, Verhoeven D, Hubens G, Van Marck E, Goovaerts G, Huyghe M, De Bruijn E A, Van Oosterom A T, Dirix L Y
Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Belgium.
Ann Oncol. 1995 Jan;6(1):59-64. doi: 10.1093/oxfordjournals.annonc.a059043.
Thymidine incorporation studies performed in animal tumour models, revealed major differences in endothelial cell proliferation when tumour tissue was compared with normal tissue. The fraction of proliferating endothelial cells is reported to be increased by a factor of 30 to 40 in tumour tissue.
To make it possible to analyze the endothelial cell proliferation in human tumours, an immunohistochemical double staining technique comprising CD31, an endothelial cell marker, and Ki-67, a proliferation marker, was developed. Endothelial cell proliferation was analysed in 21 primary human colorectal adenocarcinomas and in the adjacent mucosa.
Proliferating endothelial cells were found throughout the entire carcinoma. The mean overall endothelial cell labeling index (ECLI) was 9.9% (range, 5.4-18.0), and the labeling index of endothelial cells in areas of intense neovascularisation was even higher. Mean ECLI in the vascular hot spots was 21.0% (range, 6.8-35.0), and the mean tumour cell labeling index (TCLI) in the maximally Ki-67 immunostained areas was 78.3% (range 47.0-89.7). In 14 of 21 carcinomas, these areas were predominantly found at the luminal margin of the tumour, as were the vascular hot spots. A significant positive correlation was found between tumour vascularity, measured in the vascular hot spots, and tumour cell proliferation, measured in the maximally Ki-67 immunostained areas (p < 0.05). To analyse this relation in more detail, microvessel density (MVD), TCLI and ECLI were determined per x400 microscopic field by scanning in sequence from the luminal tumour margin to the invasive tumour base. In all tumours, the pattern of the MVD per x400 field, from the luminal margin to the tumour base, was similar to that of the TCLI and ECLI.
These findings confirm that the fraction of cycling endothelial cells is higher in human colorectal carcinoma than in the adjacent mucosa which suggests that endothelial cells are proliferating in most of the individual capillaries in tumour tissue. Regional differences in MVD correlate with differences in tumour cell proliferation in these tumours.
在动物肿瘤模型中进行的胸腺嘧啶核苷掺入研究显示，当将肿瘤组织与正常组织进行比较时，内皮细胞增殖存在重大差异。据报道，肿瘤组织中增殖内皮细胞的比例增加了30至40倍。
为了能够分析人类肿瘤中的内皮细胞增殖情况，开发了一种免疫组织化学双重染色技术，该技术包括内皮细胞标志物CD31和增殖标志物Ki-67。对21例原发性人类结肠腺癌及其相邻黏膜中的内皮细胞增殖情况进行了分析。
在整个癌组织中均发现了增殖的内皮细胞。内皮细胞总体标记指数（ECLI）的平均值为9.9%（范围为5.4 - 18.0），在新生血管密集区域内皮细胞的标记指数甚至更高。血管热点区域的平均ECLI为21.0%（范围为6.8 - 35.0），在Ki-67免疫染色最强的区域肿瘤细胞标记指数（TCLI）的平均值为78.3%（范围为47.0 - 89.7）。在21例癌组织中的14例中，这些区域主要位于肿瘤的管腔边缘，血管热点区域也是如此。在血管热点区域测量的肿瘤血管密度与在Ki-67免疫染色最强的区域测量的肿瘤细胞增殖之间存在显著正相关（p < 0.05）。为了更详细地分析这种关系，通过从肿瘤管腔边缘到浸润性肿瘤基底依次扫描，在每个400倍显微镜视野下确定微血管密度（MVD）、TCLI和ECLI。在所有肿瘤中，每个400倍视野下从管腔边缘到肿瘤基底的MVD模式与TCLI和ECLI的模式相似。
这些发现证实，人类结肠腺癌中循环内皮细胞的比例高于相邻黏膜，这表明肿瘤组织中大多数单个毛细血管中的内皮细胞在增殖。这些肿瘤中MVD的区域差异与肿瘤细胞增殖的差异相关。
