VEGFR-2 expression in malignant tumours of the canine mammary gland: a prospective survival study

Vet Comp Oncol. 2016 Sep;14(3):e83-92. doi: 10.1111/vco.12107. Epub 2014 Jun 27.

Abstract

Vascular endothelial growth factor receptor-2 (VEGFR-2) is the main receptor activated by vascular endothelial growth factor -A (VEGF-A) to promote tumour angiogenesis. Its clinical prognostic value has not been studied in canine mammary tumours (CMTs). Dogs with mammary cancer were enrolled in a survival study and the immunohistochemical expressions of VEGFR-2 and VEGF-A were analysed and associated with clinicopathological features. VEGFR-2 expression was associated with VEGF immunoreactivity in cancer cells, supporting the presence of an autocrine loop that may be involved in CMTs growth and survival. VEGFR-2 was also expressed by endothelial cells from tumour vasculature and positively associated with stromal matrix metalloproteinase-9 (MMP-9), suggesting the existence of a link between endothelial cells activation and up-regulation of matrix degrading proteins. Carcinosarcomas exhibited high VEGFR-2 expression suggesting that it may be one of the activated molecular pathways in this aggressive histological type and that VEGFR-2 inhibitors may constitute a potential treatment to improve the prognosis of these patients. Both VEGF and VEGFR-2 immunoreactivities were independent of patients' overall survival (OS) and disease-free survival (DFS).

Keywords: VEGF; VEGFR-2; cancer; canine; carcinosarcomas; mammary.

MeSH terms

  • Animals
  • Carcinoma / metabolism
  • Carcinoma / veterinary
  • Carcinosarcoma / metabolism
  • Carcinosarcoma / veterinary
  • Dog Diseases / metabolism*
  • Dogs
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Immunohistochemistry / veterinary
  • Mammary Neoplasms, Animal / metabolism*
  • Survival Analysis
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2