Breast Cancer Research and Treatment

, Volume 98, Issue 3, pp 261–266

Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density

  • Shinichi Tsutsui
  • Hiroshi Inoue
  • Kazuhiro Yasuda
  • Kosuke Suzuki
  • Hideya Takeuchi
  • Takashi Nishizaki
  • Hidefumi Higashi
  • Shoichi Era
  • Masaki Mori
Preclinical study

DOI: 10.1007/s10549-005-9157-9

Cite this article as:
Tsutsui, S., Inoue, H., Yasuda, K. et al. Breast Cancer Res Treat (2006) 98: 261. doi:10.1007/s10549-005-9157-9

Summary

Angiopoietin (Ang) is a ligand for the endothelium-specific tyrosine kinase receptor Tie-2, while a shift in the Ang-1:Ang-2 expression ratio in favor of Ang-2 was found to be associated with tumor angiogenesis. In the present study, we analyzed the immunohistochemical expression of Ang-2 in a series of 198 breast cancers, in which VEGF expression and microvessel density (MVD) were previously determined. Ang-2 expression was negative in 24 (12%), positive in 50 (25%) and strongly positive in 124 (63%) of 198 cases. A significant correlation was found between Ang-2 and VEGF expressions (p=0.0004) and between Ang-2 expression and MVD (p=0.0006), while a high MVD was found in 10 (77%) of 13 tumors with a strongly positive VEGF and positive Ang-2 expression and in 40 (71%) of 56 tumors with a strongly positive VEGF and strongly positive Ang-2 expression. Although there was no difference in the disease free survival (DFS) stratified according to Ang-2 expression alone, the 69 patients with a strongly positive VEGF and a strongly positive or positive Ang-2 expression had a significantly (p=0.0316) worse DFS than those with other combinations of VEGF and Ang-2 expressions. A multivariate analysis indicated lymph node metastasis and MVD to be independently significant prognostic factors for DFS, while the combination of VEGF and Ang-2 expressions was not a significant factor for DFS. In conclusion, the Ang-2 expression was found to be closely correlated with VEGF expression and MVD in breast cancer, while a high MVD was frequently found in tumors with a high expression of both VEGF and Ang-2. The survival analysis demonstrated a high MVD, which was induced by a high expression of both VEGF and Ang-2, to therefore have a strong prognostic significance in breast cancer.

Keywords

angiogenesis angiopoietin breast cancer microvessel density VEGF 

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Shinichi Tsutsui
    • 1
  • Hiroshi Inoue
    • 2
  • Kazuhiro Yasuda
    • 3
  • Kosuke Suzuki
    • 3
  • Hideya Takeuchi
    • 3
  • Takashi Nishizaki
    • 4
  • Hidefumi Higashi
    • 3
  • Shoichi Era
    • 5
  • Masaki Mori
    • 2
  1. 1.Department of Breast SurgeryMatsuyama Red Cross HospitalMatsuyamaJapan
  2. 2.Department of SurgeryMedical Institute of Bioregulation, Kyushu UniversityBeppuJapan
  3. 3.Department of SurgeryBeppu Medical CenterBeppuJapan
  4. 4.Department of SurgeryMatsuyama Red Cross HospitalMatsuyamaJapan
  5. 5.Department of PathologyBeppu Medical CenterBeppuJapan
  6. 6.Department of Breast SurgeryMatsuyama Red Cross HospitalMatsuyamaJapan

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