Abstract | 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.
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Authors | Ying-Chun Zhao, Xiao-Jian Ni, Yong Li, Min Dai, Zhong-Xu Yuan, Yong-Yun Zhu, Chuan-Yu Luo |
Journal | World journal of surgical oncology
(World J Surg Oncol)
Vol. 10
Pg. 165
(Aug 20 2012)
ISSN: 1477-7819 [Electronic] England |
PMID | 22906075
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- VEGFC protein, human
- VEGFD protein, human
- Vascular Endothelial Growth Factor C
- Vascular Endothelial Growth Factor D
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Topics |
- Adult
- Aged
- Breast Neoplasms
(metabolism, mortality, pathology)
- Carcinoma, Ductal, Breast
(metabolism, mortality, pathology)
- Female
- Follow-Up Studies
- Humans
- Immunoenzyme Techniques
- Lymphangiogenesis
- Lymphatic Metastasis
- Lymphatic Vessels
(metabolism, pathology)
- Middle Aged
- Neoplasm Grading
- Neoplasm Staging
- Prognosis
- Survival Rate
- Vascular Endothelial Growth Factor C
(metabolism)
- Vascular Endothelial Growth Factor D
(metabolism)
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