Molecular Diagnostics

British Journal of Cancer (2007) 97, 391–397. doi:10.1038/sj.bjc.6603875 www.bjcancer.com
Published online 3 July 2007

Prognostic analysis of tumour angiogenesis, determined by microvessel density and expression of vascular endothelial growth factor, in high-risk primary breast cancer patients treated with high-dose chemotherapy

Y Nieto1, J Woods2, F Nawaz2, A Baron3, R B Jones1, E J Shpall1 and S Nawaz2

  1. 1Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA
  2. 2Department of Pathology, University of Colorado, Denver, CO, USA
  3. 3Department of Biostatistics, University of Colorado, Denver, CO, USA

Correspondence: Dr Y Nieto, Department of Stem Cell Transplantation and Cellular Therapy, Unit 423, University of MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. E-mail: ynieto@mdanderson.org

Received 21 March 2007; Revised 12 June 2007; Accepted 12 June 2007; Published online 3 July 2007.

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Abstract

In contrast to early breast cancer, the prognostic effect of tumour angiogenesis in tumours with advanced axillary spread has been less studied. We retrospectively analysed the effect of microvessel density (MVD) and vascular endothelial growth factor (VEGF) by immunohistochemistry on the outcome of 215 patients treated uniformly within prospective trials of high-dose chemotherapy for 4–9 and greater than or equal to10 positive nodes, and followed for a median of 9 (range 3–13) years. Microvessel density was associated with epidermal growth factor receptor (EGFR) expression (P<0.001) and tumour size (P=0.001). Vascular endothelial growth factor overexpression (51% of patients) was associated with overexpression of EGFR (P=0.01) and HER2 (P<0.05), but not with MVD (P=0.3). High MVD was associated with worse relapse-free survival (74 vs 44%, P<0.001) and overall survival (76 vs 44%, P<0.001). Vascular endothelial growth factor overexpression had no effect on outcome. Multivariate analyses showed a prognostic effect of MVD independently of other known prognostic factors in this patient population. In conclusion, tumour angiogenesis, expressed as MVD, is a major independent prognostic factor in breast cancer patients with extensive axillary involvement.

Keywords:

high-risk breast cancer, angiogenesis, microvessel density, vascular endothelial growth factor, prognostic factor, high-dose chemotherapy