血管内皮生长因子及其受体与肺癌血管新生的研究

Correlation of angiogenesis with expression of vascular endothelial growth factor and its receptors in lung carcinoma

目的 研究血管内皮生长因子及其受体促进肺癌血管新生的机制 ,探讨肺癌治疗的新策略。方法 共收集 49份原发性支气管肺癌标本 ,用免疫组织化学技术检测微血管密度 (MVD)、血管内皮生长因子 (VEGF)、受体 1(Flt1)和受体 2 (KDR)在肺癌组织不同细胞成分中的表达程度。用Kaplan Meier方法比较不同血管密度患者的生存情况。结果 (1)VEGF、Flt1和KDR在肿瘤细胞、基质成纤维细胞和血管内皮细胞上均有表达。 (2 )肺癌组织MVD与肿瘤TNM分期、临床分期、病理类型和分化程度等关联不明显 ,但微血管高密度组患者生存时间短、预后差 (P <0 0 5 )。 (3)肿瘤细胞VEGF的表达程度在高、低血管密度组间差异无显著性 (P >0 0 5 ) ;而Flt1和KDR在血管高密度组的表达程度均明显高于低密度组 (P <0 0 1)。 (4 )肿瘤细胞与基质成纤维细胞VEGF的表达程度有密切关联并且具有良好的一致性。 (5 )肿瘤细胞VEGF与肿瘤细胞和血管内皮细胞KDR的表达均具有一致性 ,而与Flt1的表达却不具有一致性。结论 (1)肺癌组织MVD不受或较少受其它临床因素干扰 ,是肺癌患者评估疗效、推测预后的一个独立和良好的指标。 (2 )VEGF促进血管新生的作用不单取决于其自身 ,还必须通过受体Flt1和KDR的介导才能实现 。

Objective In order to search new therapeutic strategies, study the relationship between angiogenesis and vascular endothelial growth factor and its two receptors in lung carcinoma Methods The study consisted of 49 patients with lung carcinoma treated with curative surgery Immunohistochemistry on paraffin sections was performed with anti-human factor Ⅷ antibody to study the microvascular density(MVD), and with antibodies to VEGF, Flt1, and KDR to investigate the expression of these three proteins in different cellular compartments The survival time was compared between low MVD and high MVD groups by the Kaplan-Meier method Results (1)Expression of VEGF and its two receptors in tumor cells, stromal fibroblasts and endothelial cells was demonstrated (2)There was no significant difference between low MVD and high MVD groups in the clinical data, including TNM stage, clinical phase, pathologic type, and tumor cell differentiation( P >0 05) Survival analysis showed that the high MVD group was associated with a high risk of death (3)There was no significant difference between low MVD and high MVD groups in VEGF expression in tumor cells, but in endothelial cells both Flt1 and KDR were correlated with high microvessel count (4)The high expression of VEGF in tumor cells was correlated with that in stromal fibroblasts The level of expression in both cells was consistent (5)In both tumor cells and endothelial cells, high co-expression of VEGF and KDR was consistent, but that of VEGF and Flt1 showed inconsistency Conclusions (1)Not or rarely affected by clinical factors, MVD is a good and independent prognostic factor for patients with lung carcinoma (2)The angiogenesis is induced not only by VEGF itself, but via VEGF receptors too VEGF and its receptors thus appear to be new therapeutic targets for lung carcinoma (3)VEGF appears to be produced by both tumor cells and stromal fibroblasts (4)The result suggests that tumor expansion and angiogenesis are mainly induced by an autocrine pathway and a paracrine loop of VEGF via KDR