血管内皮生长因子-A与血管内皮生长因子-C在非小细胞肺癌中表达及与淋巴结转移的相关性

目的 探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)-A和VEGF-C在非小细胞肺癌(non-small lung cancer,NSCLC)中的表达及与淋巴管生成、转移的关系.方法 以60例肺癌组织作为实验组,20例肺正常组织作为参考组,采用免疫组织化学方法检测其中的VEGF-A和VEGF-C两种蛋白表达,以D2-40 及CD34分别标记组织淋巴管和血管中的内皮细胞,并记录淋巴管的密度,血管作为对比,结合NSCLC临床、病理参数系统分析.结果 ①肺癌组织内VEGF-A蛋白阳性的表达率为73.33%(44/60)明显高于肺正常组织25.00%(5/20)(χ2=14.7641,P=0.0001),VEGF-C蛋白的阳性表达率为83.33%(50/60) 明显高于肺正常组织30.00%(6/20)(χ2=20.3175,P =0.0001).②肺癌组织VEGF-A蛋白阳性的表达高于癌旁周围组织(χ2=4.4815,P=0.0343),癌组织内VEGF-C蛋白阳性的表达高于癌旁周围组织(χ2=8.5333,P=0.0035).③VEGF-A与VEGF-C蛋白的表达和患者的性别、年龄大小、分化的程度、肿瘤大小、组织学无关,但淋巴结转移与PTNM分期呈显著相关(χ2=6.3736,P=0.0116)和(χ2=6.6516,P=0.0099).④VEGF-A蛋白阳性组织中微淋巴管密度(microlymphatic vessel density,MLVD)显著高于阴性组织(t=-7.2735,P<0.005),VEGF-C蛋白阳性的组织中MLVD 显著高于阴性组织(t=6.9338,P<0.005).MLVD与淋巴结转移和PTNM分期显著相关(t=-12.1146,P<0.05).结论 NSCLC组织中VEGF-A与VEGF-C二者蛋白的表达可能通过促进增加淋巴管生成从而促进淋巴结的转移.因此,在NSCLC中VEGF-A和VEGF-C蛋白可作为评估淋巴结转移的重要标记因子.

The relationship of vascular endothelial growth factor-A and vascular endothelial growth factor-C with lymph node metastasis of non-small cell lung cancer

Objective To investigate the expression of vascular endothelial growth factor(VEGF)-A and VEGF-C in non-small lung cancer(NSCLC),and to explore the relationship of these molecules with lymphangiogenesis and metastasis.Methods The experimental group include 60 specimens of NSCLC.The control group included 20 samples of normal pulmonary tissue.The expression of VEGF-A and VEGF-C in specimens of NSCLC and normal pulmonary tissue were studied by immunohistochemistry.Microlymphatic vessel density (MLVD) was evaluated by immunohistochemistry ,using polyclonal antibody of D2-40 and monoclonal antibody of CD34.Combined with clinical pathologicalfeatures and diagnosis were analyzed.Results In the 60 tissue samples of NSCLC,the positive rate of VEGF-A was 73.33%(44/60),which significantly higher than those innomal pulmonary tissue 25.00%(5/20)(χ2=14.7641,P=0.0001),the positive rate of VEGF-C was 83.33%(50/60),which significantly higher than those innomal pulmonary tissue 30.00%(6/20)(χ2=20.3175,P=0.0001).The positive rate of VEGF-A was significantly higher than those in peritumoral tissues(χ2=4.4815,P=0.0343),the positive rate of VEGF-C was significantly higher than those in peritumoral tissues(χ2=8.5333,P=0.0035).The expression of VEGF-A and VEGF-C protein in NSCLC was not correlated with age,gender,size,typles of histology and degree of differentiation,but were corrected with lymph nodes metastasis and PTNM stage(χ2=6.3736,P=0.0116)and(χ2=6.6516,P=0.0099).The MLVD in the tissues with positive expression of VEGF-A、VEGF-C was significantly higher than that without VEGF-A expression(t=-7.2735,P<0.005)and VEGF-C expression(t=6.9338,P<0.005).The MLVD was corrected with lymph nodes metastasis and PTNM stage(t=-12.1146,P<0.05).Conclusion VEGF-A and VEGF-C might promotelymphatic metastasis by including lymphangiogenesis especially at the edge of lung cancer tissue.Thus,they might be used as important markers to evaluate lymphatic metastasis and prognosis of NSCLC.