文章摘要
常 超,王 平,李 琳,杨 慧,张利斌.非小细胞肺癌VEGF-C?VEGF-D?VEGFR-3表达与淋巴管生成和淋巴转移关系的研究[J].南京医科大学学报,2009,29(8):1077~1084
非小细胞肺癌VEGF-C?VEGF-D?VEGFR-3表达与淋巴管生成和淋巴转移关系的研究
Investigation on the relationship between VEGF-C,VEGF-D,VEGFR-3 and lymphangiogenesis and lymph node metastasis in non-small cell lung cancer
投稿时间:2009-04-02  
DOI:10.7655
中文关键词: 血管内皮生长因子C?D  血管内皮生长因子受体3  淋巴管内皮透明质酸受体-1  同源异型盒转录因子  非小细胞肺癌  淋巴转移
英文关键词: vascular endothelial growth factor-C,D  vascular endothelial growth factor receptor-3  lymphatic vessel endothelial hyaluronan receptor-1  the homeobox transcription factor  non-small cell lung cancer  lymphatic metastasis
基金项目:云南省应用基础研究项目(20060074M)
作者单位
常 超 昆明医学院附属昆华医院胸心外科,云南 昆明 650032 
王 平  
李 琳  
杨 慧  
张利斌  
摘要点击次数: 2200
全文下载次数: 290
中文摘要:
      目的:探讨血管内皮生长因子(VEGF)-C?-D及其受体3(VEGFR-3)在非小细胞肺癌(NSCLC)中的表达规律?与微淋巴管密度(MLVD)?淋巴转移之间的关系及其在NSCLC发生发展?预后中的意义?方法:以40例经病理确诊的NSCLC组织为实验组,以11例肺良性病变组织为对照组,采用免疫组织化学染色法对上述组织中VEGF-C?VEGF-D?VEGFR-3?淋巴管内皮透明质酸受体-1 (LYVE-1)?同源异型盒转录因子(Prox-1)蛋白的表达进行分析,并计数微淋巴管密度?结果:①NSCLC组织中VEGF-C?VEGF-D及VEGFR-3蛋白的阳性率分别为77.50%(31/40例)?67.50%(27/40例)?62.50%(25/40例),明显高于肿瘤周边组织(距肿瘤边缘100 μm区域内)及肺良性病变组织(P < 0.01)?②VEGF-C与VEGFR-3(r=0.409,P=0.005)?VEGF-D与VEGFR-3蛋白表达(r=0.492,P=0.000)均存在相关性;而VEGF-C与VEGF-D蛋白表达无相关性(r=0.256,P=0.093)?③VEGF-C?VEGF-D及VEGFR-3蛋白的表达与NSCLC患者的性别?年龄?肿瘤的大小?组织学类型?分化程度无关,但与肿瘤的淋巴结转移(P < 0.05)?PTNM分期(P < 0.05)显著相关?④NSCLC肿瘤中心组织中LYVE-1及Prox-1标记的MLVD分别为4.22±1.25?1.99±1.49,明显低于肺良性病变组织(P=0.000),而NSCLC肿瘤周边部位的MLVD显著高于肿瘤中心部位及肺良性病变组织(P=0.000)?VEGF-C?VEGF-D?VEGFR-3表达阳性的组织中,MLVD显著高于阴性组织(P < 0.05)?MLVD与肿瘤的淋巴结转移(P=0.000)?PTNM分期(P=0.000)显著相关?结论:淋巴管生成因子VEGF-C?VEGF-D及其受体VEGFR-3蛋白在NSCLC中表达显著增高,并且通过VEGF-C?VEGF-D/VEGFR-3信号通路诱导淋巴管内皮细胞新生和淋巴管生成,从而促进淋巴结转移和肿瘤生长;VEGF-C?VEGF-D及其受体VEGFR-3可能成为检测NSCLC淋巴转移和评估预后的重要分子指标;淋巴管内皮细胞特异性标志物LYVE-1?Prox-1可以较严格地区分血管和淋巴管内皮,相对精确地评价肿瘤的脉管系统?
英文摘要:
      Objective:To investigate the expression of vascular endothelial growth factor (VEGF)-C,VEGF-D and their receptor-3 (VEGFR-3) in patients with non-small cell lung cancer(NSCLC),and the relationship with lymphangiogenesis and lymph node metastasis and their clinicopathological significance. Methods:Forty specimens of the NSCLC and eleven benign pulmonary diseases were studied. The expressions of VEGF-C,VEGF-D,VEGFR-3,LVYVE-1 and Prox-1 protein in specimens of NSCLC and benign pulmonary diseases tissues were studied by immunohistochemical technique. Microlymphatic vessel density (MLVD) was counted. Results:①Among 40 cases of NSCLC,the positive rates of VEGF-C,VEGF-D and VEGFR-3 were 77.50%(31/40),67.50%(27/40)and 62.50%(25/40) respectively,which were significantly higher than those of the paraneoplastic and pulmonary benign diseases tissues(P < 0.01).②Significant correlations between VEGF-C and VEGFR-3(r=0.409,P=0.005),VEGF-D and VEGFR-3(r=0.492,P=0.000) expression were observed in NSCLC;while no correlation between VEGF-C and VEGF-D(r=0.256,P=0.093) was observed. ③The expressions of VEGF-C,VEGF-D and VEGFR-3 protein in NSCLC were not correlated with age,gender,site and dimension of lesion,types of histological and degree of differentiation,but correlated significantly with lymph node metastasis (P < 0.05) and PTNM stage(P < 0.05). ④In the center of NSCLC cancerous tissues among 40 cases,the microlymphatic vessel densities marked by LYVE-1 and Prox-1 were 4.22 ± 1.25 and 1.99 ± 1.49 respectively,which were significantly lower than those of the pulmonary benign diseases tissues(P=0.000). However,the MLVDs in cancerous invasive edge were significantly higher than those in the center of cancerous tissues and those in the pulmonary benign diseases tissues (P=0.000). The MLVDs in the positive VEGF-C,VEGF-D and VEGFR-3 groups were significantly higher than those in the negative groups (P < 0.05). MLVDs were correlated significantly with lymph node metastasis (P=0.000) and PTNM stage (P=0.000). Conclusion:Non-small cell lung cancer cells may secrete lymphangiogenetic growth factors VEGF-C,VEGF-D and their receptor VEGFR-3,which induce the growth of lymphatic vessel endothelium and lymphangiogenesis by VEGF-C,VEGF-D/VEGFR-3 signaling pathway,and further accelerate lymphatic metastasis of NSCLC. VEGF-C,VEGF-D and VEGFR-3 might be acted as molecular phenotypes of lymphangioghesis in NSCLC and important markers for evaluating lymphatic metastasis and prognosis in patients with NSCLC. As specific markers of lymphatic vessel endotheliocyte,LYVE-1 and Prox-1 could identify blood vessels and lymphatic vessels strictly and evaluate vascular system of tumor fairly exactly.
查看全文   查看/发表评论  下载PDF阅读器