Immunohistochemical Expression of Angiogenic Factors by Neoplastic Epithelial Cells Is Associated With Canine Prostatic Carcinogenesis

Vet Pathol. 2015 Jul;52(4):607-13. doi: 10.1177/0300985814549951. Epub 2014 Oct 3.

Abstract

The dog is the only species, other than humans, in which spontaneous prostatic cancer occurs; therefore, dogs are a valuable model for the study of factors that regulate tumor progression. Angiogenesis is important in the development and spread of a variety of cancers, including prostate cancer. To better define the role of cancer epithelial cells in prostate cancer neovascularization, immunohistochemical staining for angiogenic factors (vascular endothelial growth factor [VEGF], platelet endothelial cell adhesion molecule-1 [PECAM-1], Tie-2, and fibroblast growth factor-2 [FGF-2]) was performed on formalin-fixed, paraffin-embedded tissues from 10 normal prostates, 15 hyperplastic prostates, and 11 prostatic carcinomas from dogs. Normal and hyperplastic epithelial cells were negative for PECAM-1, VEGF, and Tie-2, while the same markers were expressed with a variable intensity of cytoplasmic staining by neoplastic cells. Mild to moderate FGF-2 staining was detected in all normal prostates with less than 10% of positive cells, mainly distributed in the basal layer. The percentage of FGF-2-positive hyperplastic cells was variable, with both basal and secretory cells exhibiting a perinuclear to diffuse cytoplasmic staining. The mean number of positive cells and the intensity of staining were higher in prostatic carcinomas than normal and hyperplastic prostates. Moreover, microvessel density analyzed on PECAM-1-stained slides was increased in prostate cancer compared with normal and hyperplastic prostates. Therefore, prostatic neoplastic cells are capable of simultaneous expression of various angiogenic factors and may increase tumor proliferation and angiogenesis in a paracrine and autocrine fashion.

Keywords: angiogenesis; carcinoma; dog; hyperplasia; immunohistochemistry; prostate.

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Animals
  • Carcinogenesis
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma / veterinary*
  • Dog Diseases / metabolism
  • Dog Diseases / pathology*
  • Dogs
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Immunohistochemistry / veterinary
  • Male
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology
  • Prostatic Hyperplasia / veterinary*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / veterinary*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inducing Agents
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A