title: Histopathological characterization of a syngeneic orthotopic murine bladder cancer model.
abstract: OBJECTIVE
  We developed and characterized by histopathology and immunohistochemistry a syngeneic murine bladder tumor model derived from the MB49 tumor cell line.
  
  
  METHODS
  Bladder tumor implantation was achieved by intravesical instillation of 5 x 105 MB49 tumor cells in C57BL/6 mice. A chemical lesion of the bladder was performed in order to promote intravesical tumor implantation. The bladder wall lesion was accomplished by transurethral instillation of silver nitrate (AgNO3). After 15 days, the animals were sacrificed, examined macroscopically for intravesical tumor and bladder weight. Histology and immunohistochemistry were performed using cytokeratin 7 (CK7), carcinoembrionic antigen (Dako-CEA), p53 and c-erbB2 oncoprotein (Her2/neu).
  
  
  RESULTS
  Twenty-nine out of 30 animals (96.7%) developed intravesical tumors in a 15-day period. Macroscopically, the mean bladder weight was 0.196g (0.069-0.538g), 10 to 15 times the normal bladder weight. The immunohistochemical analysis showed significant membrane expression of CEA and CK7: a similar finding for human urothelial cancer. We also characterized absence of expression of p53 and anti-Her2/neu in the murine model.
  
  
  CONCLUSIONS
  High tumor take rates were achieved by using the chemical induction of the bladder tumor. Although electric cauterization is widely described in the literature for syngeneic orthotopic animal models, the technique described in this study represents an alternative for intravesical bladder tumor implantation. Moreover, the histopathology and immunohistochemical analysis of the murine bladder tumor model derived from the MB49 cell line showed a resemblance to human infiltrating urothelial carcinoma, allowing clinical inference from experimental immunotherapy testing.
authors.affiliation: Division of Urology, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Daher C
authors.initials: DC
authors.lastname: Chade
authors.forename: Priscila M
authors.initials: PM
authors.lastname: Andrade
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Borra
authors.forename: Katia R
authors.initials: KR
authors.lastname: Leite
authors.forename: Enrico
authors.initials: E
authors.lastname: Andrade
authors.forename: Fabiola E
authors.initials: FE
authors.lastname: Villanova
authors.forename: Miguel
authors.initials: M
authors.lastname: Srougi
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D053552:Keratin-7 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053552:Keratin-7; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53