VEGF-D在乳腺癌淋巴管生成中的作用及与预后的关系

Role of VEGF-D in lymphangiogenesis of breast cancer and relationship with prognosis

目的探讨血管内皮生长因子D(VEGF-D)在乳腺癌淋巴管生成中的作用及其与临床病理指标及预后的关系。方法采用免疫组化法检测85例原发性乳腺癌VEGF-D的表达,以Podoplanin标记淋巴管内皮、计数淋巴管密度(LVD),采用RT-PCR法检测VEGF-D mRNA的表达。分析上述指标与临床病理指标及预后的关系。结果免疫组化检测显示,VEGF-D蛋白表达阴性5例(5.88%)、"+"17例(20%)、"++"34例(40%)、"+++"22例(25.88%)、"++++"7例(8.24%),其表达与淋巴结转移、临床分期相关(P<0.01),且导致较差的生存率(P<0.05)。LVD于不同表达程度的VEGF-D组间有显著差异(P<0.01),且随着VEGF-D表达的增加,LVD有上升的趋势。RT-PCR检测显示,VEGF-D mRNA在乳腺癌中的表达显著高于对照组(P<0.01),且其表达与淋巴结转移、临床分期和LVD相关(P<0.05)。结论VEGF-D在乳腺癌中具有一定的诱导淋巴管生成的作用,并与肿瘤的淋巴侵袭转移及预后相关。

Objective To evaluate the role of vascular endothelial growth factor-D （VEGF-D） in lymphangiogenesis of breast cancer, and investigate its relationship with some clinicopathological parameters and prognosis. Methods VEGF-D expression was detected in 85 cases with primary breast carcinoma by immunohistochemistry, and VEGF-D mRNA was detected by RT-PCR. Podoplanin monoclonal antibody was used to mark lymphatic endothelial cell and lymphatic vessel density （LVD） was counted. The relationship among the aboved parameters, clinicopathological parameters and prognosis was analysed. Results It was revealed by immunohistochemistry that VEGF-D expression was ranked by 5 levels： negative, n =5（5.88% ） ; ＂ ＋＂, n =17（20% ） ; ＂ ＋＋＂ , n =34（40% ） ; ＂ ＋＋＋ ＂ , n =22 （25.88%） , and ＂ ＋＋＋＋ ＂, n = 7 （8.24%）. VEGF-D expression was associated with tumor lymph node metastasis and TNM clinical stage （P 〈0.01 ）, and led to a worse outcome（ P 〈 0.05）. LVD differed significantly between different expression levels of VEGF-D （P 〈 0.01 ）. Moreover, LVD increased with the VEGF-D expression level. It was indicated by RT-PCR that VEGF-D mRNA expression was significantly higher than that of control （ P 〈 0.01 ） , and was significantly associated with tumor lymph node metastasis, TNM clinical stage and LVD （P 〈0.05）. Conclusion VEGF-D may induce lymphangiogenesis, and may be associated with lymph node invasion and prognosis in breast cancer.