ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma

Cancer. 2002 Jun 1;94(11):2855-61. doi: 10.1002/cncr.10553.

Abstract

Background: The angiogenic factor vascular endothelial growth factor (VEGF)-A plays an important role in breast cancer progression. However, the involvement of VEGF-C and VEGF-D, two newer members of the VEGF family, in breast carcinoma and their relationship with clinicopathologic parameters have not been clearly demonstrated.

Methods: In this study, the expression levels of VEGF-A, VEGF-C, and VEGF-D protein in 107 breast carcinoma cases and 22 nonmalignant breast tissue samples were examined by immunohistochemistry and quantitated by image analysis.

Results: Higher expression of VEGF-C and VEGF-D was found in breast carcinomas than in nonmalignant breast tissue samples. Moreover, expression of VEGF-A, VEGF-C, and VEGF-D was significantly and positively correlated with ErbB2 expression. High levels of VEGF-A expression were associated with shorter disease-free survival (DFS). Patients with tumors expressing high levels of VEGF-C or VEGF-D showed a notable trend for worse DFS, however, it was not statistically significant. The combination of VEGF-A and VEGF-C status predicted survival better than either marker alone.

Conclusions: Our study suggests that expression of the angiogenic and lymphangiogenic factors (i.e., VEGFs) might be regulated at least in part by ErbB2. In addition, the combination of VEGF-A and VEGF-C status may better predict prognosis of patients with breast carcinoma than VEGF-A alone.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Endothelial Growth Factors / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Middle Aged
  • Neck
  • Receptor, ErbB-2 / metabolism*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D

Substances

  • Endothelial Growth Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D
  • Receptor, ErbB-2