MacLean–Mueller Prize Prix MacLean–Mueller AN ANIMAL MODEL OF BENIGN BILE-DUCT STRICTURE, SCLEROSING CHOLANGITIS AND CHOLANGIOCARCINOMA AND THE ROLE OF EPIDERMAL GROWTH FACTOR RECEPTOR IN DUCTAL PROLIFERATION

Correspondence and reprint requests to: Dr. Rona E. Cheifetz, c/o Department of Surgery, Faculty of Medicine, 910 West 10th Ave., 3rd Floor, Vancouver BC V5Z 4E3 OBJECTIVE: To adapt an animal model of benign bile-duct stricture, sclerosing cholangitis and cholangiocarcinoma in order to determine if the expression of epidermal growth factor receptor (EGFr) could be used to differentiate these lesions. DESIGN: A prospective control study with blinded interpretation of liver biopsy histology and immunohistochemical staining as the criterion standards. SETTING: A university-affiliated research centre. SUBJECTS: Male Syrian Golden hamsters (40 for benign duct stricture, 29 for sclerosing cholangitis and 27 for cholangiocarcinoma). 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 subcutaneous injections of 500 mg/kg of di-isopropanolnitrosamine for 10 weeks followed by ligation of the common bile duct with 6-0 catgut for cholangiocarcinoma. 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 benign or atypical biliary ductal proliferation, including adenoma and carcinoma formation. The presence or absence of immunohistochemical staining for EGFr. RESULTS: Benign ductal proliferation without atypia was seen in 15 of 21 animals in the bile-duct-stricture group that were sacrificed, in 15 of 24 animals in the sclerosing cholangitis group and in 17 of 18 animals in the cholangiocarcinoma group. Atypical proliferation was seen in 13 of 18 animals with cholangiocarcinoma but not in the other two groups. The differential occurrence of atypical ductal proliferation was statistically significant (p < 0.00001) for both groups. No evidence of EGFr expression was found in any group. CONCLUSION: Although the animal model was valid histologically for comparing benign and malignant biliary disease, EGFr does not play a role in biliary ductal proliferation and so cannot be used to differentiate between benign and malignant lesions.