肺癌血管内皮生长因子(VEGF)及其受体KDR、Flt1的表达与患者预后的关系

Expression of vascular endothelial growth factor (VEGF) and its receptors KDR, Flt1 in lung cancer and their relationship to prognosis

背景与目的血管内皮生长因子(VEGF)及其受体与肺癌血管生成关系密切,但与肺癌患者预后的关系尚不明确。本研究的目的是对VEGF及其受体KDR、Flt1的表达与肺癌患者预后的关系进行探讨。方法应用免疫组织化学PV-9000法检测75例具有完整随访资料的肺癌标本中VEGF及其受体KDR、Flt1的表达。结果VEGF、KDR、Flt1在肺癌组织中的表达较为广泛,主要位于肿瘤细胞、血管内皮细胞、纤维母细胞胞质中,且其表达呈异质性,肺癌组织周边部及坏死区周围的肺癌细胞中表达较强,三者在肿瘤细胞中的阳性率均高于间质纤维母细胞(P<0.01,P<0.02,P<0.02)。肺癌细胞及纤维母细胞VEGF、KDR和Flt1的阳性表达率在术后不同生存时间的三组间差异均具统计学意义(P<0.01,P<0.01,P<0.01;P<0.01,P<0.01,P<0.05);肺癌细胞VEGF、KDR、Flt1阳性组患者的生存时间均显著低于各相应指标阴性者(P<0.0001,P<0.0005,P<0.0005)。肺癌细胞中VEGF与Flt1受体的表达呈正相关(P<0.01),纤维母细胞中VEGF与肺癌细胞中Flt1受体的表达呈正相关(P<0.01),纤维母细胞中VEGF与KDR、Flt1表达分别呈正相关(P<0.01,P<0.01)。结论VEGF可能是促进肺癌细胞生长的重要因子,主要以自分泌途径并附以旁分泌途径通过Flt1发挥作用;VEGF及受体KDR、Flt1对肺癌患者的预后有重要的影响作用。

Background and objective It is well known that vascular endothelial growth factor （VEGF） and its receptors are closely related to tumor angiogenesis, but the exact relationship with patients＇ prognosis is unclear till now. The aim of this study is to explore the expression of VEGF and its receptors KDR, Flt1 in pulmonary carcinoma and their relationship with patients＇ prognosis. Methods The expression of VEGF, KDR and Flt1 was examined immunohistochemically by PV-9000 method in 75 cases of pulmonary carcinoma with complete follow-up records. Results There was an extensive expression of VEGF, KDR and Flt1, mainly in the cytoplasm of tumor cells （TCs）, fibroblasts （FBs）, and endothelial cells. The distribution of VEGF, KDR and Flt1 was heterogeneous, mainly located at periphery of the tumor mass or necrosis. The positive rate of VEGF, KDR and Flt1 in the TCs was all significantly higher than that in the FBs （P〈0.01, P〈0.02, P 〈0.02）. Both in TCs and FBs, the positive expression of VEGF, KDR and Flt1 was related to the postoperative survival of patients （P〈0.01, P〈0.01, P〈0.01; P〈0.01, P〈0.01, P〈0.05）. The survival time in patients with positive VEGF, KDR or Flt-1 in TCs was significantly lower than that in those with corresponding negative one respectively （P〈0. 0001, P〈0. 0005, P〈0. 0005）. There was a positive correlation between VEGF and Flt1 in TCs （P〈0.01）, between VEGF in FBs and Flt1 in TCs （P〈0.01）, and also between VEGF and KDR or Flt1 in FBs （P〈0.01, P〈0.01）. Conclusion VEGF may act as a considerable promoting growth factor on tumor cells via Flt1, mainly in autocrine and less in paracrine manner. VEGF, KDR and Flt1 may exert important roles in prognosis of patients with pulmonary carcinoma.