Kitadai Y, Haruma K, Tokutomi T, Tanaka S, Sumii K, Carvalho M, Kuwabara M, Yoshida K, Hirai T, Kajiyama G, Tahara E
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Clin Cancer Res. 1998 Sep;4(9):2195-200.
The purpose of this study was to determine the angiogenic profile of human esophageal carcinomas. The expression of vascular endothelial growth factor (VEGF) was examined in 6 esophageal carcinoma cell lines and 119 human esophageal carcinoma tissues by Northern blot analysis and immunohistochemistry, respectively. Immunohistochemistry using antibodies against CD34 (endothelial cell specific) was carried out on archival specimens, and microvessels were quantitated by counting vessels in a x200 field in the most vascular area of the tumor. All of the cell lines constitutively expressed VEGF mRNA at various levels. A total of 71 of 119 (59.7%) tumors showed intense VEGF immunoreactivity in the cytoplasm of cancer cells. Vessel count was significantly higher in the VEGF-positive tumors than it was in the VEGF-negative tumors. VEGF expression correlated with the depth of tumor invasion, tumor stage, venous invasion, and lymphatic invasion. The survival rate of patients with high vessel density in the tumor was significantly worse than that of patients with low vessel density in the tumor. There was a tendency for poorer prognosis in the group with VEGF-positive tumors compared with that of the group with VEGF-negative tumors. Overall, these results suggest that VEGF is associated with tumor progression by stimulating angiogenesis in human esophageal carcinoma.
本研究的目的是确定人食管癌的血管生成特征。分别通过Northern印迹分析和免疫组织化学检测了6种食管癌细胞系和119例人食管癌组织中血管内皮生长因子(VEGF)的表达。对存档标本进行了使用抗CD34抗体(内皮细胞特异性)的免疫组织化学检测,并通过在肿瘤血管最丰富区域的200倍视野中计数血管来定量微血管。所有细胞系均组成性地以不同水平表达VEGF mRNA。119例肿瘤中有71例(59.7%)在癌细胞胞质中显示出强烈的VEGF免疫反应性。VEGF阳性肿瘤中的血管计数显著高于VEGF阴性肿瘤。VEGF表达与肿瘤浸润深度、肿瘤分期、静脉浸润和淋巴浸润相关。肿瘤血管密度高的患者的生存率显著低于肿瘤血管密度低的患者。与VEGF阴性肿瘤组相比,VEGF阳性肿瘤组有预后较差的趋势。总体而言,这些结果表明VEGF通过刺激人食管癌中的血管生成与肿瘤进展相关。