Histological Characterization of Biliary Intraepithelial Neoplasia with respect to Pancreatic Intraepithelial Neoplasia

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. 1. 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]. The classification is applicable to flat atypical epithelial lesions in the intrahepatic large bile ducts and the extrahepatic bile ducts, and it is also applied to lesions in the gallbladder according to the current World Health Organization (WHO) classification for tumors of the digestive system [3]. BilIN is a concept that is proposed based on the morphological resemblance to pancreatic intraepithelial neoplasia (PanIN). Similar to PanIN, BilIN is classified into three grades according to the degree of cytological and architectural atypia: BilIN-1 (low-grade lesions), BilIN-2 (intermediate-grade lesions), and BilIN-3 (high-grade lesions, carcinoma in situ). Using the BilIN classification, there is increasing evidence that molecular and genetic alterations accumulate during the progression of BilIN to cholangiocarcinoma [4–7]. Since the biliary tract and pancreas share a common developmental process as