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 intra- and 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 peri- and 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.