Seto Takashi, Higashiyama Masahiko, Funai Hiroko, Imamura Fumio, Uematsu Kazutsugu, Seki Nobuhiko, Eguchi Kenji, Yamanaka Takeharu, Ichinose Yukito
Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan.
Lung Cancer. 2006 Jul;53(1):91-6. doi: 10.1016/j.lungcan.2006.02.009. Epub 2006 May 11.
Angiogenesis plays an important role in tumorigenesis and has attracted interest as a potential target in cancer treatment.
We examined the prognostic value of the expression of vascular endothelial growth factor (VEGF) and of the VEGF receptors (VEGFRs) fms-like tyrosine kinase receptor-1 (flt-1) and kinase insert domain-containing receptor (KDR) in non-small-cell lung cancer (NSCLC). Sixty patients with surgical stage I NSCLC who had not undergone induction therapy or adjuvant therapy were selected from among 170 patients with NSCLC who had undergone surgery from January to December 1995. Specimens obtained at surgical resection were subjected to immunohistological staining, and the relationship between postoperative outcome and the expression of VEGF and its receptors was investigated. All patients included in the analysis had been followed up for 5 years or longer or until death.
Patients with tumors expressing VEGF or KDR tended to have poorer outcomes, and VEGF expression and KDR expression were positively correlated. In contrast, flt-1 expression was not correlated with VEGF expression or outcome. Outcomes were poor in patients with tumors positive for both VEGF and VEGFRs. Multivariate analysis identified expression of both flt-1 and KDR and VEGF and KDR as possible independent prognostic factors.
Our results suggest that expression of VEGF and VEGFR are associated with a poor prognosis via autocrine and paracrine growth stimulation of cancer cells. Moreover, tumors expressing both flt-1 and KDR may have greater malignant potential and are associated with a poor prognosis.
血管生成在肿瘤发生过程中起重要作用，作为癌症治疗的潜在靶点已引起关注。
我们检测了血管内皮生长因子（VEGF）及其受体——fms样酪氨酸激酶受体-1（flt-1）和含激酶插入结构域受体（KDR）在非小细胞肺癌（NSCLC）中的表达对预后的影响。从1995年1月至12月接受手术的170例NSCLC患者中选取60例手术分期为I期且未接受诱导治疗或辅助治疗的患者。对手术切除获取的标本进行免疫组织化学染色，研究术后转归与VEGF及其受体表达之间的关系。纳入分析的所有患者均随访5年或更长时间或直至死亡。
肿瘤表达VEGF或KDR的患者预后往往较差，且VEGF表达与KDR表达呈正相关。相比之下，flt-1表达与VEGF表达或预后无关。VEGF和VEGFRs均呈阳性的肿瘤患者预后较差。多因素分析确定flt-1和KDR同时表达以及VEGF和KDR同时表达可能为独立的预后因素。
我们的结果表明，VEGF和VEGFR的表达通过癌细胞的自分泌和旁分泌生长刺激与不良预后相关。此外，同时表达flt-1和KDR的肿瘤可能具有更大的恶性潜能且与不良预后相关。
