title: Cyclooxygenase-2 promotes angiogenesis in pTa/T1 urothelial bladder carcinoma but does not predict recurrence.
abstract: OBJECTIVE
  To investigate the effect of cyclooxygenase-2 (COX-2) on microvessel density (MVD) and on the clinical prognosis in patients with non-muscle invasive urothelial carcinoma of the bladder, as COX-2 expression is significantly greater in epithelial tumours and there is increasing evidence that COX-2 might contribute to tumour neovascularization.
  
  
  METHODS
  We assessed tumour samples from 110 patients undergoing transurethral resection for primary pTa/pT1 bladder carcinoma (pTa, 84; pT1, 26; grade 1, 22; grade 2, 81; grade 3, seven). Paraffin sections were assessed immunohistochemically using antibodies against COX-2, CD34 (endothelial cells) and CD105 (proliferating vessels). COX-2 expression was quantified by the number of stained cells (negative, +, ++) and the MVD calculated as vessels per field.
  
  
  RESULTS
  Of the 110 tumours, 45 (41%) had no immunostaining for COX-2, 40 had faint staining with at least isolated positive cells (+) and 25 stained ++. COX-2 positive tumours had significantly greater vascularization for proliferating vessels. In COX-2 negative tumours the MVD was 22.1, identified by CD34 immunostaining, and 3.4 for proliferating vessels (CD105), whereas COX-2 positive tumours had a MVD of 18.3 (CD34), and of 5.8, respectively (CD105). Complete follow-up data were available in 91 patients; after a mean follow-up of 25 months, 18 (20%) had tumour recurrences. There was no significant difference in the recurrence rates or disease-free survival between COX-2-positive (19%, 25.6 months) or -negative patients (21%, 25.2 months).
  
  
  CONCLUSIONS
  These results confirm the involvement of COX-2 in angiogenesis in bladder cancer, as COX-2 promoted blood vessel proliferation in the tumour zone, and indicate the usefulness of COX-2-inhibiting drugs in preventing and treating superficial bladder cancer.
authors.affiliation: Department of Urology, University of Hamburg.
authors.forename: M G
authors.initials: MG
authors.lastname: Friedrich
authors.forename: M I
authors.initials: MI
authors.lastname: Toma
authors.forename: S
authors.initials: S
authors.lastname: Petri
authors.forename: H
authors.initials: H
authors.lastname: Huland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D008833:Microcirculation; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009389:Neovascularization, Pathologic / Q000209:etiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000201:enzymology
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases