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

AbstractBACKGROUND:
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.
AuthorsYing-Chun Zhao, Xiao-Jian Ni, Yong Li, Min Dai, Zhong-Xu Yuan, Yong-Yun Zhu, Chuan-Yu Luo
JournalWorld journal of surgical oncology (World J Surg Oncol) Vol. 10 Pg. 165 (Aug 20 2012) ISSN: 1477-7819 [Electronic] England
PMID22906075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • VEGFC protein, human
  • VEGFD protein, human
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D
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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