AN ANIMAL-MODEL OF BENIGN BILE-DUCT STRICTURE, SCLEROSING CHOLANGITISAND CHOLANGIOCARCINOMA AND THE ROLE OF EPIDERMAL GROWTH-FACTOR RECEPTOR IN DUCTAL PROLIFERATION

OBJECTIVE: To adapt an animal model of benign bile-duct stricture, scl erosing cholangitis and cholangiocarcinoma in order to determine if th e expression of epidermal growth factor receptor (EGFr) could be used to differentiate these lesions. DESIGN: A prospective control study wi th blinded interpretation of liver biopsy histology and immunohistoche mical staining as the criterion standards. SETTING: A university-affil iated research centre. SUBJECTS: Male Syrian Golden hamsters (40 for b enign duct stricture, 29 for sclerosing cholangitis and 27 for cholang iocarcinoma). INTERVENTIONS: Ligation of the common bile duct with 6-0 catgut for benign duct stricture; injection of the biliary tree with 0.15 mL of formalin for sclerosing cholangitis; and weekly subcutaneou s injections of 500 mg/kg of di-isopropanolnitrosamine for 10 weeks fo llowed by ligation of the common bile duct with 6-0 catgut for cholang iocarcinoma. Routine histologic preparation of liver biopsies obtained at autopsy 10 weeks postoperatively then immunohistochemical staining of specimens for EGFr. MAIN OUTCOME MEASURES: The development of beni gn or atypical biliary ductal proliferation, including adenoma and car cinoma formation. The presence or absence of immunohistochemical stain ing for EGFr. RESULTS: Benign ductal proliferation without atypia was seen in 15 of 21 animals in the bile-duct-stricture group that were sa crificed, in 15 of 24 animals in the sclerosing cholangitis group and in 17 of 18 animals in the cholangiocarcinoma group. Atypical prolifer ation was seen in 13 of 18 animals with cholangiocarcinoma but not in the other two groups. The differential occurrence of atypical ductal p roliferation was statistically significant (p < 0.00001) for both grou ps. No evidence of EGFr expression was found in any group. CONCLUSION: Although the animal model was valid histologically for comparing beni gn and malignant biliary disease, EGFr does not play a role in biliary ductal proliferation and so cannot be used to differentiate between b enign and malignant lesions.