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

World Journal of Surgical Oncology

Chuan-Yu Luo²  Yong-Yun Zhu²  Zhong-Xu Yuan³  Min Dai¹  Yong Li¹  Xiao-Jian Ni³  Ying-Chun Zhao² 

[1] Department of Pathology, The Second People’s Hospital of Wuhu Affiliated with Wannan Medical College, 231 Jiuhuashan Road, Wuhu, 241000, China;Department of Breast Surgery, The Second People’s Hospital of Wuhu Affiliated with Wannan Medical College, 231 Jiuhuashan Road, Wuhu, 241000, China;Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

关键词: VEGF-D;    VEGF-C;    Metastasis;    Lymphangiogenesis;    Breast cancer;   

Others  :  827406
DOI  :  10.1186/1477-7819-10-165

 received in 2012-06-01, accepted in 2012-07-27,  发布年份 2012

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2012 Zhao et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 3.

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