Abstract

Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar/perihilar and extrahepatic cholangiocarcinoma. BilIN represents the process of multistep cholangiocarcinogenesis and is the biliary counterpart of pancreatic intraepithelial neoplasia (PanIN). This study was performed to clarify the histological characteristics of BilIN in relation to PanIN. Using paraffin-embedded tissue sections of surgically resected specimens of cholangiocarcinoma associated with BilIN and pancreatic ductal adenocarcinoma associated with PanIN, immunohistochemical staining was performed using primary antibodies against MUC1, MUC2, MUC5AC, cyclin D1, p21, p53, and S100P. For mucin staining, Alcian blue pH 2.5 was used. Most of the molecules examined here showed similar expression patterns in BilIN and PanIN, in which their expression tended to increase along with the increase in atypia of the epithelial lesions. Significant differences were observed in the increase in mucin production and the expression of S100P in PanIN-1 and the expression of p53 in PanIN-3, when compared with those in BilIN of a corresponding grade. These results suggest that cholangiocarcinoma and pancreatic ductal adenocarcinoma share, at least in part, a common carcinogenic process and further confirm that BilIN can be regarded as the biliary counterpart of PanIN.

Highlights

  • Cholangiocarcinoma that arises under conditions of chronic biliary diseases such as hepatolithiasis often undergoes the multistep carcinogenesis process [1]

  • The classification is applicable to flat atypical epithelial lesions in the intrahepatic large bile ducts and the extrahepatic bile ducts, and it is applied to lesions in the gallbladder according to the current World Health Organization (WHO) classification for tumors of the digestive system [3]

  • Similar to pancreatic intraepithelial neoplasia (PanIN), Biliary intraepithelial neoplasia (BilIN) is classified into three grades according to the degree of cytological and architectural atypia: BilIN-1, BilIN-2, and BilIN-3

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Summary

Introduction

Cholangiocarcinoma that arises under conditions of chronic biliary diseases such as hepatolithiasis often undergoes the multistep carcinogenesis process [1]. Biliary intraepithelial neoplasia (BilIN) is known as a premalignant lesion of cholangiocarcinoma that represents the multistep cholangiocarcinogenesis [2]. Since the biliary tract and pancreas share a common developmental process as well as morphological characteristics as duct systems, it is plausible that some biliary and pancreatic diseases show similar pathological features and biological behaviors [8]. We showed that intraductal papillary neoplasm of the bile duct (IPNB) and intraductal papillary mucinous neoplasm (IPMN) of the pancreas, as well as mucinous cystic neoplasm (MCN) of the biliary tract and pancreas, exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process of the tumors [10], where all these tumors were classified as premalignant lesions according to the current WHO classification. This study was conducted to clarify the histological characteristics of BilIN with respect to PanIN

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