Expression of Wisp-1, β-catenin, TGF-β1 and Smad4 in gold hamster induced intrahepatic cholangiocarcinoma and their significance / 临床与实验病理学杂志

ABSTRACT

Purpose To establish a golden hamster model of intrahepatic cholangiocarcinoma (ICC) using BOP [N-nitrosobis (2-oxo-propyl) amine] and to explore the protein expression of Wisp-1,β-catenin, TGF-β1 and Smad4 in ICC and their relationship with the tumorigenesis. Methods 57 female golden hamsters aged 8 to 9 weeks (39 in experimental group, 18 in control group), the experi-mental animals were subjected to subcutaneous injection of BOP, the control group was injected with saline. The liver was removed and paraffin sections were prepared for histopathological observation. The protein expression of Wisp-1,β-catenin, TGF-β1 and Smad4 was detected by immunohistochemistry (IHC) in these blocks. Results Most of the animals in the experimental group (29/39) developed ICC, part of the animal (8/39) developed bile duct dysplasia, 1 developed focal bile duct hyperplasia, and 1 was not found bile duct hyperplasia. The positive expression rates of four protein markers in ICC, bile duct dysplasia and normal intrahepatic bile duct tissues were Wisp-1,79. 3%, 87. 5% and 5. 0%,β-catenin, 96. 6%, 100. 0% and 15. 0%, Smad4, 96. 6%, 100. 0% and 25. 0%, TGF-β1, 62. 1%, 12. 5% and 5. 0%, respectively. The positive expression rates of Wisp-1, beta-catenin and Smad4 protein in both the ICC and the tissue of bile duct dysplasia were higher than that of normal intrahepatic bile duct tissue ( P<0. 001 ) , The positive ex-pression of TGF-β1 in the ICC tissue was higher than that of normal intrahepatic bile duct tissue and bile duct dysplasia (P<0. 001). Conclusions The study showed that BOP can induce a golden hamster model of ICC and provides a reliable animal model for the study of ICC. The high expression of Wisp-1,β-catenin, TGF-β1 and Smad4 in BOP-induced intrahepatic cholangiocarcinoma is closely re-lated to occurrence, development and infiltration of ICC.