Fujimoto K, Hosotani R, Wada M, Lee J U, Koshiba T, Miyamoto Y, Tsuji S, Nakajima S, Doi R, Imamura M
Department of Surgery and Surgical Basic Science, Kyoto University, Japan.
Eur J Cancer. 1998 Aug;34(9):1439-47. doi: 10.1016/s0959-8049(98)00069-0.
Tumour angiogenesis, as assayed by microvessel density (MVD), and the expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) have become established as important prognostic indicators for many tumour types. In this study, MVD and the expression of VEGF and PD-ECGF were examined by immunohistochemical staining of 50 pancreatic cancer tissues, and the relationships between either MVD or the expression of these two angiogenic factors and the clinicopathological features, including survival, were analysed. The expression of VEGF and PD-ECGF proteins were confirmed by Western blot analysis and VEGF mRNA isoforms were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in five pancreatic cancer cell lines. Twenty-eight (56%) of 50 pancreatic cancers were positive for VEGF protein in cancer cells, and 16 (32%) showed strong PD-ECGF staining in cancer and infiltrating cells. VEGF121 and VEGF165 were identified as the predominant species produced in pancreatic cancer cells. The overexpression of VEGF and PD-ECGF protein significantly correlated with high MVD (P = 0.002, 0.044, respectively). Advanced stage of disease was significantly more frequent in patients with high MVD (P = 0.025). No significant association was found between the expression of VEGF or PD-ECGF and clinicopathological features, except for tumour histology. The expression of PD-ECGF correlated with poor survival (P = 0.011), but MVD and VEGF expression were not found to be useful for the prediction of overall survival. This study suggests that VEGF and PD-ECGF may play an important role in tumour angiogenesis, and that PD-ECGF expression seems to be useful for establishing prognoses for pancreatic cancer.
通过微血管密度（MVD）测定的肿瘤血管生成以及血管内皮生长因子（VEGF）和血小板衍生内皮细胞生长因子（PD-ECGF）的表达，已成为多种肿瘤类型重要的预后指标。在本研究中，通过对50例胰腺癌组织进行免疫组化染色来检测MVD以及VEGF和PD-ECGF的表达，并分析MVD或这两种血管生成因子的表达与包括生存率在内的临床病理特征之间的关系。通过蛋白质印迹分析证实了VEGF和PD-ECGF蛋白的表达，并通过逆转录聚合酶链反应（RT-PCR）在五种胰腺癌细胞系中测定了VEGF mRNA亚型。50例胰腺癌中有28例（56%）癌细胞VEGF蛋白呈阳性，16例（32%）癌细胞及浸润细胞中PD-ECGF染色强。VEGF121和VEGF165被确定为胰腺癌细胞产生的主要亚型。VEGF和PD-ECGF蛋白的过表达与高MVD显著相关（分别为P = 0.002和0.044）。高MVD患者疾病晚期的发生率显著更高（P = 0.025）。除肿瘤组织学外，未发现VEGF或PD-ECGF的表达与临床病理特征之间存在显著关联。PD-ECGF的表达与较差的生存率相关（P = 0.011），但未发现MVD和VEGF表达对预测总生存率有用。本研究表明，VEGF和PD-ECGF可能在肿瘤血管生成中起重要作用，并且PD-ECGF表达似乎对胰腺癌的预后评估有用。
