血管内皮生长因子受体-3与非小细胞肺癌淋巴结转移的相关性研究

摘要

Objective To identify the clinical significance of vascular endothelial growth factor receptor (VEGFR)-3 expression to lymph node metastasis in patients with non-small cell lung cancer (NSCLC).Method Lung tissues samples and 196 lymph nodes from 52 NSCLC patients were included in the assay; lung tissues and 8 lymph nodes from 10 patients with lung diseases other than cancer were included as control. A semi quantitative multiplex RT-PCR technology was applied to measure the quantity of VEGFR-3 mRNA; VEGFR-3 protein expression level was assessed immunohistochemically. The lymphatic vessel sum was counted and micro lymphatic vessel density(MLVD) Was calculated.Result The VEGFR-3 mRNA level in lymph node tissue among the group with lymph node metastasis was significantly lower than that of the group without lymph node metastasis (P<0.05). The VEGFR-3 mRNA level in lung tumor tissue from NSCLC patients was no difference between lymph node metastasis group and lymph node non-metastasis group (P>0.05). In the lymph node metastasis group, there was no different between metastasized lymph nodes and non-metastasized lymph nodes (P>0.05). When VEGFR-3 mRNA level is concerned. Morphologically, VEGFR-3 immunoreactivity mainly localized in cytoplasm of lymphatic endothelial cells and some cancer cells. Micro lymphatic vessel density (MLVD) is significant higher in lung tissue around the tumor than in the tumor tissue; significant higher in the lymph node metastasis group than in the lymph node non-metastasis group. MLVD and lymph node metastasis were much higher in VEGFR-3 protein positive group than the negative group.Conclusion VEGFR-3 expression levels may correlate with lymph node metastasis in NSCLC patients. MLVD is a key factor of lymphatic vessel metastasis in NSCLC. The enhanced MLVD indicates lymph angiogenesis and lymphantie node metastasis, and may be an important predictor for tumor activity monitoring and prognosis.%目的 检测血管内皮生长因子受体-3(vascular endothelial growth factor receptor-3,VEGFR-3)在非小细胞肺癌癌组织及淋巴结组织中的表达水平,探讨VEGFR-3与非小细胞肺癌淋巴结转移的相关性.方法 收集非小细胞肺癌患者术后肺组织标本52例,淋巴结196枚;良性肺疾病患者肺组织标本10例,淋巴结8枚.分别应用半定量反转录聚合酶链反应(RT-PCR)及免疫组化法检测肺组织和淋巴结组织中的VEGFR-3 mRNA及蛋白的表达量,同时测定微淋巴管密度.结果 VEGFR-3 mRNA在淋巴结转移阳性组的淋巴结组织中的表达水平低于淋巴结转移阴性组的淋巴结(P<0.05),而在淋巴结转移阳性组的肺癌组织中的表达水平与淋巴结转移阴性组肺癌组织比较无显著区别(P>0.05).在淋巴结转移阳性组中,VEGFR-3 mRNA在阳性淋巴结与阴性淋巴结中的表达水平无显著区别(P>0.05).VEGFR-3不仅在淋巴管内皮细胞表达,在小血管内皮及肿瘤细胞胞浆也有表达.VEGFR-3阳性管计数在癌周组织显著高于癌组织,在淋巴结转移组显著高于淋巴结未转移组.VEGFR-3蛋白表达阳性组与阴性组比较,微淋巴管密度及淋巴结转移都显著升高.结论 VEGFR-3 mRNA及蛋白的表达水平与肺癌淋巴结转移有显著相关性,在预测肺癌的淋巴结转移、完善分子分期、指导临床治疗上有重要意义.微淋巴管密度是肿瘤淋巴道转移的关键因素,其升高预示着淋巴管生成和淋巴结转移的发生,可作为肿瘤监测和预后的指示因子.