Vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGFR-3 and D2-40 expressions in primary breast cancer: Association with lymph node metastasis

BACKGROUND: Two members of the vascular endothelial growth factor (VEGF) family, VEGF-C and -D, are known as lymphangiogenic growth factors and play an important role in tumor lymphangiogenesis via activation of the VEGF receptor (VEGFR)-3, which is expressed in lymphatic endothelial cells. D2-40 is a specific antibody for lymphatic vessel density (LVD). OBJECTIVES: In the present study, we have aimed to evaluate whether intraand peri-tumoral D2-40-positive lymphatic vessels affect lymph node metastasis and to investigate the relationship between LVD and lymph node metastasis in breast cancer. MATERIAL AND METHODS: We have evaluated the relationships between lymph node metastasis and VEGF-C, VEGF-D, VEGFR-3 and D2-40 expressions in breast cancer cells using immunohistochemistry. VEGF-C, VEGF-D and VEGFR-3 expression were found in tumor cells in the majority of the cases (83.75, 97.5 and 95%, respectively). RESULTS: There was a significant positive relationship between VEGF-D expression and lymph node metastasis (p < 0.05) however no significant association was found in VEGF-C and VEGFR-3 expressions. It was found that patients with high-expression of VEGF-D have a high level of both periand intra-tumoral LVD compared to those with low expression of VEGF-D (p < 0.05). CONCLUSIONS: Our results support that examination of VEGF-D expression in breast cancer cells may be beneficial in the identification of lymph node metastasis.