The angiogenic switch for vascular endothelial growth factor-A and cyclooxygenase-2 in prostate carcinoma: correlation with microvessel density, androgen receptor content and Gleason grade

Urol Int. 2011;87(4):464-9. doi: 10.1159/000329289. Epub 2011 Sep 10.

Abstract

Objective: Angiogenesis is essential for tumor growth and metastasis; however, angiogenic factors are not uniformly expressed in prostate carcinoma. Our aim was to determine the expression of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) in prostate carcinomas in relation to intratumoral microvessel density (MVD), tumor grade and androgen receptor (AR) status.

Materials and methods: The expression of AR, VEGF-A and COX-2 was immunohistochemically evaluated in 24 benign prostatic hyperplasia (BPH) and 139 prostate carcinoma cases. MVD was evaluated by CD34 immunostaining.

Results: Nuclear AR expression was inversely related to tumor grade (p < 0.001). MVD was strongly related to tumor grade, VEGF-A and COX-2 (p < 0.001 in all comparisons). VEGF-A expression increased with tumor grade (p < 0.01) and was inversely related to stromal AR expression. COX-2 was present in both BPH and prostate carcinoma, but its expression increased with tumor grade (p < 0.01). High-grade neoplasms presented low-to-moderate VEGF staining intensity compared to strong COX-2 expression.

Conclusions: Both VEGF-A and COX-2 expression is positively correlated with tumor grade and MVD. However, in Gleason 8-10 tumors, VEGF expression is moderate while COX-2 immunostaining is intense, suggesting a possible switch in the role of these two angiogenic factors in poorly differentiated neoplasms.

MeSH terms

  • Analysis of Variance
  • Animals
  • Antigens, CD34 / analysis
  • Biomarkers, Tumor / analysis*
  • Carcinoma / blood supply
  • Carcinoma / chemistry*
  • Carcinoma / pathology
  • Cell Differentiation
  • Cyclooxygenase 2 / analysis*
  • Greece
  • Immunohistochemistry
  • Male
  • Microvessels / pathology*
  • Neoplasm Grading
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Prostatic Hyperplasia / metabolism*
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / blood supply
  • Prostatic Neoplasms / chemistry*
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / analysis*
  • Vascular Endothelial Growth Factor A / analysis*

Substances

  • AR protein, human
  • Antigens, CD34
  • Biomarkers, Tumor
  • Receptors, Androgen
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2
  • PTGS2 protein, human