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

Objective 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 nonmetastatic 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.