Uchida S, Shimada Y, Watanabe G, Tanaka H, Shibagaki I, Miyahara T, Ishigami S, Imamura M
Department of Surgery & Surgical Basic Science, Graduate School of Medicine, Kyoto University, Japan.
Br J Cancer. 1998 May;77(10):1704-9. doi: 10.1038/bjc.1998.281.
Vascular endothelial growth factor (VEGF) affects malignant tumours by promoting angiogenesis. The tumour-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on oesophageal carcinoma and the connection between VEGF and p53. One hundred and nine resected oesophageal squamous cell carcinomas were examined. VEGF expression was analysed by immunohistochemical staining. Sixty-five tumours (59.6%, 65 out of 109) were classified as VEGF positive. A significant correlation was found between the VEGF expression and both the depth of invasion (P = 0.0001) and lymph node metastasis (P < 0.0001). With regard to p53, we compared the expression of VEGF with the mutation of p53, examined using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing in tumour samples obtained from 36 patients who we have reported previously. The VEGF expression was significantly correlated to p53 mutation (P = 0.0291). To evaluate the angiogenesis, microvascular density (MVD) was counted, and endothelial cells were stained immunohistochemically using anti-CD34 monoclonal antibody against 29 cases with invasion limited to the submucosal layer. The average MVD had a tendency to correlate to VEGF expression (P = 0.1626). The prognoses of patients with VEGF-positive primary tumours were significantly worse than for those with VEGF-negative primary tumours (P = 0.0077). We have assumed that VEGF contributes to aggressive characteristics in oesophageal carcinomas and that VEGF expression might be affected by p53 status.
血管内皮生长因子(VEGF)通过促进血管生成影响恶性肿瘤。肿瘤抑制基因p53被认为可调节VEGF。我们研究了VEGF对食管癌的影响以及VEGF与p53之间的联系。对109例切除的食管鳞状细胞癌进行了检查。通过免疫组织化学染色分析VEGF表达。65例肿瘤(59.6%,109例中的65例)被分类为VEGF阳性。发现VEGF表达与浸润深度(P = 0.0001)和淋巴结转移(P < 0.0001)均显著相关。关于p53,我们将VEGF的表达与p53的突变进行了比较,使用聚合酶链反应-单链构象多态性(PCR-SSCP)和直接测序对36例我们之前报道过的患者的肿瘤样本进行检测。VEGF表达与p53突变显著相关(P = 0.0291)。为评估血管生成,对29例浸润仅限于黏膜下层的病例计数微血管密度(MVD),并使用抗CD34单克隆抗体对内皮细胞进行免疫组织化学染色。平均MVD有与VEGF表达相关的趋势(P = 0.1626)。VEGF阳性原发性肿瘤患者的预后明显比VEGF阴性原发性肿瘤患者差(P = 0.0077)。我们推测VEGF促成了食管癌的侵袭性特征,并且VEGF表达可能受p53状态的影响。