title: Expression of epidermal growth factor receptor, apomucins, matrix metalloproteinases, and p53 in rat and human cholangiocarcinoma: appraisal of an animal model of cholangiocarcinoma.
abstract: OBJECTIVE
  We sought to determine the expression of molecular markers in an animal model of cholangiocarcinoma compared with those in human cholangiocarcinoma.
  
  
  BACKGROUND
  Cholangiocarcinoma is a rare disease characterized by early intrahepatic and extrahepatic spread, which seriously limits the efficacy of surgery. Establishing an experimental model to study the cholangiocarcinogenesis is desirable.
  
  
  METHODS
  Sprague-Dawley rats weighing 300 +/- 50 g were used for the study group. The animals were given 0.3% thioacetamide in tap water continuously. Thirty mass-forming peripheral cholangiocarcinoma patients also were studied. Expression of epidermal growth factor receptor (EGFR), MUC1, MUC2, MUC5AC, MMP-2, MMP-9, and p53 in both human and experimental rat cholangiocarcinoma was examined using immunohistochemistry.
  
  
  RESULTS
  Using thioacetamide 0.3% as a hepatoxin to induce cholangiocarcinoma in rats, microfoci of cancerous cells were detected from 12 weeks, and all experimental rats displayed diffuse mass-forming cholangiocarcinoma after 24 weeks. EGFR was strongly expressed in 14 (47%) of 30 human cholangiocarcinoms and 24 (100%) of 24 rat cholangiocarcinomas, respectively. MUC1 was strongly expressed in all human and rat cholangiocarcinomas, whereas MUC2 and MUC5AC were focally and weakly expressed. MMP-2 and MMP-9 were strongly expressed in 22 (73%) of 30 human cholangiocarcinomas and 24 (100%) of 24 rat cholangiocarcinomas, respectively. p53 overexpression was detected in 9 (30%) of 30 human cholangiocarcinoma and none of the rat cholangiocarcinoma, respectively.
  
  
  CONCLUSIONS
  The expression of EGFR, apomucins, MMPs, and p53 in rat cholangiocarcinoma was strongly homologous to human cholangiocarcinoma. Thioacetamide-induced cholangiocarcinoma in rats provides an excellent model for investigating cholangiocarcinogenesis in vivo.
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan. tsy471027@adm.cgmh.org.tw
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Jan
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.forename: Jun-Nan
authors.initials: JN
authors.lastname: Yeh
authors.forename: Horng-Ren
authors.initials: HR
authors.lastname: Yang
authors.forename: Miin-Fu
authors.initials: MF
authors.lastname: Chen
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D009077:Mucins; D016159:Tumor Suppressor Protein p53; D013853:Thioacetamide; D066246:ErbB Receptors; D020782:Matrix Metalloproteinases