Histological and immunohistological findings in biliary intraepithelial neoplasia arising from a background of chronic biliary disease compared with liver cirrhosis of non-biliary aetiology

Aims: Hitherto, biliary intraepithelial neoplasia (BilIN) has been described in chronic biliary disease but rarely in non-biliary liver cirrhosis (LC). Intraepithelial neoplasia of the pancreas shows alterations in the expression of cell cycle and mucin core proteins. The aim of this study was to evaluate BilIN and reactive biliary lesions in biliary disease and non-biliary LC. Methods and results: BilIN was found in 51% (33 of 65) of liver tissue cases of biliary disease, and in 11% (34 of 310) of the LC group. Immunohistologically, MUC5AC, an 'early phase' protein, and Ki67, reflecting 'late phase' expression, were identified with increasing degrees of dysplasia in both groups, but that expression was significantly higher in the biliary disease group. 'Early phase' cell cycle proteins, p16 (decrease) and p21 (increase) altered in both biliary and LC groups with increasing degrees of dysplasia. Conclusions: We found BilIN in the large bile ducts of hepatitis B virus- and hepatitis C virus-related LC as well as in cases related to a biliary aetiology. The LC group was significantly less likely to show changes in the expression of MUC5AC and proliferative activity than the biliary group. Alterations in p16 and p21 reflected increasing degrees of dysplasia in both groups.