title: Urothelial differentiation in vesicoureteric reflux and other urological disorders of childhood: a comparative study.
abstract: OBJECTIVE
  The strong familial basis of vesicoureteric reflux (VUR) is well recognised, however little progress has been made in identifying the causative genes. In this study we have investigated whether human vesicoureteric reflux (VUR) is associated with the aberrant expression of urothelial differentiation-associated antigens in view of the VUR phenotype of the Uroplakin IIIa (UPIIIa) "knockout" mouse.
  
  
  METHODS
  Samples of urothelium were collected from 13 children with primary VUR, four children with secondary VUR and from seven children with non-refluxing disorders of the urinary tract. Immunohistochemistry was used to assess the expression of five uroplakin (UP) and cytokeratin (CK) differentiation-restricted antigens, UPIa, UPIb, UPIIIa, CK13 and CK20. Samples were ranked blind according to immunohistochemical patterns relating to the differentiation-associated distributions of the five antigens and the results were analysed statistically using the Kruskal-Wallis test.
  
  
  RESULTS
  No objective differences in urothelial morphology or the expression of the five differentiation antigens were discernable in the urothelium of children with primary VUR, when compared with urothelium of children with a range of other pathology including VUR associated with duplication or pelvic renal ectopia, VUR secondary to outflow obstruction and non-refluxing upper tract obstruction. The p-values ranged from 0.168-0.651 and were not considered statistically significant.
  
  
  CONCLUSIONS
  The results indicate that primary VUR is not associated with any major, collective abnormality of urothelial differentiation in man. In particular our findings provide no support for the suggestion that abnormalities of UPIIIa expression are implicated in the aetiology of human primary VUR.
authors.affiliation: The Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, University of York, and Department of Urology, St. James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Mary A E
authors.initials: MA
authors.lastname: Garthwaite
authors.forename: David F M
authors.initials: DF
authors.lastname: Thomas
authors.forename: Ramnath
authors.initials: R
authors.lastname: Subramaniam
authors.forename: Jens
authors.initials: J
authors.lastname: Stahlschmidt
authors.forename: Ian
authors.initials: I
authors.lastname: Eardley
authors.forename: Jennifer
authors.initials: J
authors.lastname: Southgate
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D053554:Keratin-20; D007633:Keratins / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D014570:Urologic Diseases / Q000378:metabolism*; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib; D019459:Urothelium / Q000378:metabolism*; D014718:Vesico-Ureteral Reflux / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; C507499:KRT20 protein, human; D053554:Keratin-20; D008562:Membrane Glycoproteins; C086451:UPK1A protein, human; C086452:UPK1B protein, human; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib; D007633:Keratins