非小细胞肺癌中VEGF-C、VEGF-D、VEGFR-3表达与微淋巴管密度的关系

Relationship of VEGF-C / D and VEGFR-3 expression and lymphatic vascular microvascular density in non-small cell lung cancer

目的探讨血管内皮生长因子C、D(VEGF-C、D)及血管内皮生长因子受体3(VEGFR-3)在非小细胞肺癌(NSCLC)中的表达的规律与微淋巴管密度、淋巴结转移之间的关系及其在NSCLC发生发展、预后中的意义。方法采用免疫组化SP法检测40例NSCLC患者癌组织、癌旁组织、146枚淋巴结及11例正常肺组织中VEGF-C、VEGF-D、VEG-FR-3、淋巴管内皮透明质酸受体-1(LYVE-1)蛋白的表达,并计数微淋巴管数量。结果 VEGF-C、VEGF-D和VEGFR-3蛋白阳性率在NSCLC癌组织中明显高于正常肺组织及癌旁组织(P<0.05);在有淋巴结转移组的淋巴结中VEGF-C、VEGF-D和VEGFR-3蛋白表达率高于无淋巴结转移组(P<0.05);在TNM分期中,NSCLC癌组织中VEGF-C、VEGF-D和VEGFR-3在Ⅲ期+Ⅳ期的表达明显高于Ⅰ期+Ⅱ期的表达(P<0.05);但在NSCLC癌组织中VEGF-C、VEGF-D和VEGFR-3的表达与年龄、性别、肿瘤大小、组织类型、分化程度上差异无统计学意义。NSCLC癌组织与正常肺组织和癌旁组织中微淋巴管密度差异有统计学意义(P<0.01);NSCLC癌组织中微淋巴管密度在VEGF-C、VEGF-D和VEG-FR-3阳性表达组与阴性组比较,差异有统计学意义(P<0.05);NSCLC癌组织中微淋巴管密度在有淋巴结转移组与无淋巴结转移组分别为(13.17±0.72)和(9.38±0.93)(P<0.01);NSCLC癌组织中微淋巴管密度Ⅰ期+Ⅱ期与Ⅲ期+Ⅳ期比较差异有统计学意义(P<0.01);但NSCLC癌组织中微淋巴管密度与性别、年龄、肿瘤大小、组织学类型和分化程度无关。结论 VEGF-C、VEGF-D及其受体VEGFR-3蛋白在NSCLC中的表达显著增加,说明VEGF-C、VEGF-D及其受体VEGFR-3可能成为检测NSCLC转移和评估的重要分子指标;淋巴管内皮细胞特异性标志物LYVE-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。

Objective To observe 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 lym- phangiogenesis and lymph node metastasis and their clinicopathological significance. Methods Immunohistochmis- try method was used to detect the expression of VEGF-C, VEGF-D,VEGFR-3 and LYVE-1 in tumour specimens, adjacent tissues and 146 lymph nodes of 40 cases with NSCLC, and normal lung tissues from 11 cases, and its lym- phatic vascular microvascular density（LVMD）. Results The positive rate of VEGF-C, VEGF-D and VEGFR-3 in NSCLC was significantly higher than that in normal lung tissues and adjacent tissues （ P 〈 0. 05 ） ; VEGF-C, VEGF-D and VEGFR-3 expression were significantly higher in patients with lymph node metastasis than in those without lymph node metastasis（ P 〈 0. 05 ） ; In TNM stage VEGF-C, VEGF-D and VEGFR-3 expression were signif- icantly higher in patients with Ⅲ ＋ Ⅳ stage than Ⅰ ＋ Ⅱ stage in NSCLC （P 〈 0. 05 ）. There was no significant rela- tionship with age, sex, tumor size, histological type and differentiation in NSCLC. It had significant difference to LVMD of the NSCLC tissue and normal lung tissues and adjacent tissues（P 〈0.01 ）. LVMD of the NSCLC tisse in lymph node metastasis group and non-metastasis group was （ 13.17 ± 0. 72） and （9.38 ± 0. 93 ） respectively, and it had significant difference（P 〈0. 01 ）;there had difference of LVMD of Ⅲ ＋ Ⅳ stage and Ⅰ ＋ Ⅱ stage compared with NSCLC （P 〈 0. 01 ）. There was no significant difference of LVMD in age, sex, tumor size, histological type and differentiation. Conclusion NSCLD cells may secrete lymphangiogenetic growth factors VEGF-C, VEGF-D and their receptor VEGFR-3, and further accelerate lymphatic metastasis of NSCLC. VEGF-C, VEGF-D and VEGFR-3 might act as molecular phenotypes of lymphangioghesis in NSCLC and important markers for evaluating lymphatic metastasis and prognosis in patients with NSCLC. As specific marker of lymphatic vessel endotheliocyte, LYVE-I could be used to identify blood vessels and lymphatic vessels and evaluate vascular system of tumor fairly exactly.