title: 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.
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.
  
  
  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.
authors.affiliation: Department of Anatomy, University of Patras, School of Medicine, Patras, Greece. kogyftop @ yahoo.gr
authors.forename: K
authors.initials: K
authors.lastname: Gyftopoulos
authors.forename: K
authors.initials: K
authors.lastname: Vourda
authors.forename: G
authors.initials: G
authors.lastname: Sakellaropoulos
authors.forename: P
authors.initials: P
authors.lastname: Perimenis
authors.forename: A
authors.initials: A
authors.lastname: Athanasopoulos
authors.forename: E
authors.initials: E
authors.lastname: Papadaki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D002454:Cell Differentiation; D051546:Cyclooxygenase 2 / Q000032:analysis*; D006115:Greece; D007150:Immunohistochemistry; D008297:Male; D055806:Microvessels / Q000473:pathology*; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
chemical_list: C410798:AR protein, human; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human