Expression of epidermal growth factor receptor, apomucins, matrix metalloproteinases, and p53 in rat and human cholangiocarcinoma: appraisal of an animal model of cholangiocarcinoma.
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.
Jan
Yi-Yin
YY
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan. tsy471027@adm.cgmh.org.tw
Yeh
Ta-Sen
TS
Yeh
Jun-Nan
JN
Yang
Horng-Ren
HR
Chen
Miin-Fu
MF
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*
D009077:Mucins; D016159:Tumor Suppressor Protein p53; D013853:Thioacetamide; D066246:ErbB Receptors; D020782:Matrix Metalloproteinases