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

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)261-266
Number of pages6
JournalBreast Cancer Research and Treatment
Volume98
Issue number3
DOIs
Publication statusPublished - Aug 1 2006

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Angiopoietin-2
Carcinoma, Ductal, Breast
Microvessels
Vascular Endothelial Growth Factor A
Disease-Free Survival
Breast Neoplasms
Neoplasms
Angiopoietins
Angiopoietin-1
Receptor Protein-Tyrosine Kinases

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Angiopoietin 2 expression in invasive ductal carcinoma of the breast : Its relationship to the VEGF expression and microvessel density. / Tsutsui, Shinichi; Inoue, Hiroshi; Yasuda, Kazuhiro; Suzuki, Kosuke; Takeuchi, Hideya; Nishizaki, Takashi; Higashi, Hidefumi; Era, Shoichi; Mori, Masaki.

In: Breast Cancer Research and Treatment, Vol. 98, No. 3, 01.08.2006, p. 261-266.

Research output: Contribution to journalArticle

Tsutsui, Shinichi ; Inoue, Hiroshi ; Yasuda, Kazuhiro ; Suzuki, Kosuke ; Takeuchi, Hideya ; Nishizaki, Takashi ; Higashi, Hidefumi ; Era, Shoichi ; Mori, Masaki. / Angiopoietin 2 expression in invasive ductal carcinoma of the breast : Its relationship to the VEGF expression and microvessel density. In: Breast Cancer Research and Treatment. 2006 ; Vol. 98, No. 3. pp. 261-266.
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AU - Yasuda, Kazuhiro

AU - Suzuki, Kosuke

AU - Takeuchi, Hideya

AU - Nishizaki, Takashi

AU - Higashi, Hidefumi

AU - Era, Shoichi

AU - Mori, Masaki

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AB - 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.

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