非小细胞肺癌VEGF-C表达与淋巴管生成和淋巴转移关系的研究

Study on relationship between VEGF-C and lymphangiogenesis and lymph node metastasis in non-small cell lung cancer

背景与目的近年来的研究表明,血管内皮生长因子C(VEGFC)通过与其配体(VEGFR3)的结合介导肿瘤淋巴管生成,是形成肿瘤淋巴道转移的最重要因素。淋巴道转移是非小细胞肺癌(NSCLC)常见的主要扩散途径。基于此,本研究用新的淋巴管内皮标志物podoplanin检测NSCLC组织中淋巴管,用淋巴管密度(LVD)表示淋巴管生成情况,探讨NSCLC内VEGFC表达与淋巴管生成和淋巴转移的关系。方法收集66例NSCLC和8例炎性假瘤组织标本,应用免疫组化检测VEGFC、podoplanin的表达,计算VEGFC阳性表达率及淋巴管密度值,分析两者的关系。结果NSCLC组织内VEGFC阳性表达率(75.8%)显著高于肺炎性假瘤(12.5%)(P<0.01),高中分化(76.3%)和低分化(75.0%)之间无显著性差异(P>0.05),淋巴结阳性组中VEGFC阳性率(86.5%)显著高于淋巴结阴性组(62.1%)(P<0.05)。NSCLC组织内LVD(20.4±5.9)显著高于肺炎性假瘤(10.9±4.9)(P<0.01);VEGFC阳性组LVD(21.3±6.0)显著高于VEGFC阴性组(17.7±5.1)(P<0.05),淋巴结阳性组LVD(21.9±5.9)显著高于淋巴结阴性组(18.5±5.5)(P<0.05)。结论淋巴管生成可能是NSCLC淋巴结转移的重要因素,VEGFC参与NSCLC淋巴管生成,从而促进淋巴结转移。

Background and Objective Increasing evidences have shown that vascular endothelial growth factor C （VEGF-C） is involved in the tumor lymphangiogenesis via combining with its ligand, vascular endothelial growth factor receptor-3 （VEGFR-3）, which is the most important factor contributing to lymph node metastasis. Futhermore, lymph node metastasis is the most familiar metastatic pathway in non-small cell lung cancer （NSCLC）. Based on this knowledge, the present study aims to explore the relationship between VEGF C and lymphangiogenesis and lymph node metastasis in NSCLC with the use of podoplanin, a novel lymphatic vessel endothelium marker to detect lymphatic vessel. Methods The expression of VEGF-C and podoplanin were detected in 66 paraffin sections of NSCLC and 8 inflammatory pseudotumor tissues by immunohistochemistry （SP）. Assessments of podoplanin＋lymphatic vessel density （LVD） and positive rates of VEGF-C were performed and their relationship was analysed. Results The positive rate of VEGF-C in the inflammatory pseudotumor group （12.5%） was significantly lower than that in the NSCLC group （75.8%） （P〈0.01）, the positive rate of VEGF-C in the positive lymph node group was significantly higher than that in the negative lymph node metastasis group （86.5% vs 62.1%, P〈0. 05） and there was no difference between the well differentiated group and the poor differentiated group （76.3 % vs 75.0 %, P〉0.05）. LVD in the positive VEGFC group was significantly higher than that in the negative VEGFC group （21.3±6.0 vs 17. 7±5. 1, P〈 0.05）, LVD in the inflammatory pseudotumor group （10. 9±4. 9） was distinctly lower than that in the NSCLC group （20.4±5.9） （P〈0.01） and compared with the negative lymph node metastasis group （18.5±5.5）, LVD （21.9±5.9） in the positive lymph node metastasis group increased significantly （P〈0.05）. Conclusion Lymphangiogenesis is a significant factor for tumor lymphatic metastasis, VEGF-C may mediate lymphatic metastasis of NSCLC by the way of inducing lymphangiogenesis.