Lymphangiogenesis induced by VEGF-C and VEGF-D promotes metastasis and a poor outcome in breast carcinoma: a retrospective study of 61 cases

Clin Exp Metastasis. 2008;25(7):717-25. doi: 10.1007/s10585-008-9180-4. Epub 2008 May 30.

Abstract

Purpose: To evaluate lymphangiogenesis in patients with breast carcinoma, explore the underlying mechanism, and study the relationship between lymphangiogenesis and progression of breast carcinoma.

Methods: Sixty-one cases of breast carcinoma with complete clinical and pathological data were analyzed. Using an anti-podoplanin monoclonal antibody, an immunohistochemical study was made of all specimens to detect lymphatic vessel density (LVD) and to investigate its clinicopathological and prognostic value. VEGF-C and VEGF-D were observed by RT-PCR and immunostaining to investigate their clinicopathological and prognostic values and their relationship with lymphangiogenesis.

Results: LVD in breast carcinoma (6.28+/-3.73) was significantly higher than in benign mammary lesions (0.50+/-1.27), P<0.01 and was significantly associated with lymphatic metastasis and high TNM stage, P<0.01. The level of VEGF-C and VEGF-D expression was also significantly higher in breast carcinomas than in benign mammary lesions, P<0.01. LVD increased significantly with higher expression of VEGF-C and VEGF-D, P<0.01. Patients with high expression of VEGF-C and VEGF-D were observed to be more likely to have a bad outcome, P<0.05.

Conclusions: Lymphangiogenesis was significantly associated with lymph node metastasis, high TNM, and poor outcome in breast carcinoma. LVD may serve as a predictor of lymph node metastasis and a prognostic factor in breast carcinoma. VEGF-C and VEGF-D play an important role in lymphangiogenesis making the carcinoma more aggressive and leading to a poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Lymphangiogenesis*
  • Middle Aged
  • Neoplasm Metastasis
  • RNA, Messenger / analysis
  • Retrospective Studies
  • Vascular Endothelial Growth Factor C / analysis
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / physiology*
  • Vascular Endothelial Growth Factor D / analysis
  • Vascular Endothelial Growth Factor D / genetics
  • Vascular Endothelial Growth Factor D / physiology*

Substances

  • RNA, Messenger
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D