Smad4和VEGF-C的表达与乳腺癌淋巴管生成之间的关系

Correlation of VEGF-C and Smad4 expression with lymphangiogenesis in human breast cancer

目的观察Smad4和血管内皮生长因子(VEGF)-C在人乳腺癌组织内的表达情况,分析Smad4和VEGF-C的表达与乳腺癌淋巴管生成及淋巴结转移之间的关系。方法取乳腺癌病例56例,其中,淋巴结转移组35例,无淋巴结转移组21例。应用免疫组化法和Western blot技术观察Smad4和VEGF-C在乳腺癌组织内的表达。以D2-40作为淋巴管内皮特异性标记物,检测乳腺癌组织内淋巴管生成情况。结果 Smad4在无淋巴结转移组的表达率明显高于其在有淋巴结转移组的表达率,Smad4表达阳性组的淋巴管数密度(LVD)明显低于Smad4表达阴性组。而VEGF-C在淋巴结转移组的表达率明显高于其在无淋巴结转移组的表达率。Smad4的表达与VEGF-C的表达呈显著的负相关性(r=-0.314)。Western blot检测结果表明,VEGF-C蛋白在有淋巴结转移乳腺癌组织中的表达量高于其在无淋巴结转移乳腺癌组织内的表达量,而Smad4在有淋巴结转移乳腺癌组织内的表达量明显低于其在无淋巴结转移组的表达量。结论 VEGF-C在乳腺癌淋巴管的发生及淋巴结转移中发挥重要作用,与Smad4的表达呈负相关,Smad4可能通过调节VEGF-C蛋白的表达而抑制乳腺癌淋巴管生成和淋巴道转移的作用。

Objeeti,ce To investigate the effects of Smad4 and vascular endothelial growth factor（VEGF）-C in lymphangiogenesis and lymph node metastasis, we observed the expression of Smad4 and VEGF-C in human breast cancer. Methods Fifty-six paraffin-embedded specimens from patients with breast cancer were divided into lymph node metastatic group（n=35） and nonmetastatie group（n=21）. The expressions of Smad4 and VEGF-C were detected by immunohistochemical stain and Western blot. D2-40 was used as the specific lymphatic endothelial marker for detecting lymphangiogenesis in breast cancer. Results The expression level of Smad4 in nonmetastatic group was significantly higher than that in lymph node metastatic group. The lymphatic vessel density（LVD） in Smad4 positive group was significantly decreased than that in Smad4 negative group. The expression level of VEGF-C in lymph node metastatic group was significantly higher than that in nonmetastatic group. Smad4 expression was negatively correlated with VEGF-C expression （r=-0.314）. Conclusion VEGF-C plays an important role in tumor lymphangiogenesis and lymph node metastasis in breast cancer, with negative correlation with Smad4 expression, indicating that Smad4 may inhibit tumor lymphangiogenesis and lymph node metastasis through regulating the expression of VEGF-C protein in breast cancer.