title: Evaluation of vascular endothelial growth factors A, C and D as indicators of lymphangiogenesis and angiogenesis in invasive and non-invasive urothelial carcinoma bladder.
abstract: OBJECTIVE
  To study the immunohistochemical expression of vascular endothelial growth factors in urothelial tumours of bladder and its possible association with tumour characteristics and microvessel density.
  
  
  METHODS
  The cross-sectional descriptive study was conducted at the Histopathology Department of the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from July 2011 to December 2012, and comprised cases of non-invasive and invasive urothelial tumours of the bladder. The microvessel density and expression of vascular endothelial growth factors A, C, D were evaluated by immunohistochemistry. Specimens of transurethral bladder biopsies and surgical resection were examined. The cases were classified into non-invasive (stage pTa ) and invasive groups as well as low-grade and high-grade groups. The presence of in-situ component was evaluated in each category. To assess the microvessel density, highly vascularised foci ('hot spots') after immuno-staining with CD34 were quantified for number of vessels per square millimetre and for vascular surface area density. No distinction was made between lymphatic and blood vessels. Vascular endothelial growth factor staining was scored semi-quantitatively.
  
  
  RESULTS
  The study examined 100 histopathology specimens, including 90(90%) transurethral bladder biopsies and 10(10%) surgical resection specimens of bladder. There were 45(45%) non-invasive (stage pTa) cases and 55(55%) invasive (stage pT1-4) cases. Besides, there were 43(43%) low-grade (grades 1 and 2) cases, and 57(57%) high-grade (grade 3) cases. Vascular endothelial growth factors A, C and D staining scores showed positive association with stage (p=0.02;p<0.01; p<0.01)and grade (p=0.007;p=0.004; p=0.002) of the tumour. Tumours with in-situ component showed association with number of vessels per square millimetre (p<0.01) and vascular surface area density (p=0.02).
  
  
  CONCLUSIONS
  Parameters like vascular endothelial growth factor and microvessel density need to be studied further for selection of cases with potential for targeted therapy.
authors.affiliation: Department of Pathology/Histopathologist, PNS-Shifa, Karachi.
authors.forename: Muhammad Tahir
authors.initials: MT
authors.lastname: Khadim
authors.affiliation: Baqai Medical University, Karachi.
authors.forename: Syed Azhar
authors.initials: SA
authors.lastname: Ahmed
authors.affiliation: Rai Medical College, Sargodha.
authors.forename: Farooq Ahmad
authors.initials: FA
authors.lastname: Khan
authors.affiliation: Department of Microbiology, AFIP, Rawalpindi.
authors.forename: Aamer
authors.initials: A
authors.lastname: Ikram
authors.affiliation: Department of Pathology, PNS Shifa, Karachi.
authors.forename: Shagufta Yousaf
authors.initials: SY
authors.lastname: Shaikh
mesh_terms: D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D042583:Lymphangiogenesis; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; C467486:VEGFC protein, human; C579459:VEGFD protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D
keywords: Urothelial carcinoma, Papillary urothelial neoplasm, Microvessel density, Lymphangiogenesis, Angiogenesis, Vascular endothelial growth factors.