Peritumoral lymphangiogenesis induced by vascular endothelial growth factor C and D promotes lymph node metastasis in breast cancer patients

• Published in: World journal of surgical oncology 2012-08, Vol.10 (1), p.165-165, Article 165
• Main Authors: Zhao, Ying-Chun, Ni, Xiao-Jian, Li, Yong, Dai, Min, Yuan, Zhong-Xu, Zhu, Yong-Yun, Luo, Chuan-Yu
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Antibodies; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer patients; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - mortality; Carcinoma, Ductal, Breast - pathology; Chemotherapy; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Immunohistochemistry; Lymphangiogenesis; Lymphatic Metastasis; Lymphatic system; Lymphatic Vessels - metabolism; Lymphatic Vessels - pathology; Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Risk factors; Survival Rate; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor C - metabolism; Vascular Endothelial Growth Factor D - metabolism; VEGF-C; VEGF-D; Viral antibodies
• ISSN: 1477-7819; 1477-7819
• DOI: 10.1186/1477-7819-10-165

Mounting clinical and experimental data suggest that the migration of tumor cells into lymph nodes is greatly facilitated by lymphangiogenesis. Vascular endothelial growth factor (VEGF)-C and D have been identified as lymphangiogenic growth factors and play an important role in tumor lymphangiogenesis. The purpose of this study was to investigate the location of lymphangiogenesis driven by tumor-derived VEGF-C/D in breast cancer, and to determine the role of intratumoral and peritumoral lymphatic vessel density (LVD) in lymphangiogenesis in breast cancer. The expression levels of VEGF-C/D were determined by immunohistochemistry, and intratumoral LVD and peritumoral LVD were assessed using immunohistochemistry and the D2-40 antibody in 73 patients with primary breast cancer. The associations of intratumoral LVD and peritumoral LVD with VEGF-C/D expression, clinicopathological features and prognosis were assessed. VEGF-C and D expression were significantly higher in breast cancer than benign disease (P < 0.01). VEGF-C (P < 0.001) and VEGF-D (P = 0.005) expression were significantly associated with peritumoral LVD, but not intratumoral LVD. Intratumoral LVD was associated with tumor size (P = 0.01). Peritumoral LVD was significantly associated with lymph node metastasis (LNM; P = 0.005), lymphatic vessel invasion (LVI; P = 0.017) and late tumor,node, metastasis (TNM) stage (P = 0.011). Moreover, peritumoral LVD was an independent risk factor for axillary lymph node metastasis, overall survival and disease-free survival in multivariate analysis. This study suggests that tumor-derived VEGF-C/D induce peritumoral lymphangiogenesis, which may be one mechanism that leads to lymphatic invasion and metastatic spread. Peritumoral LVD has potential as an independent prognostic factor in breast cancer patients.