Cellular senescence in biliary pathology. Special emphasis on expression of a polycomb group protein EZH2 and a senescent marker p16INK4a in bile ductular tumors and lesions.

[cholangiocarcinoma]

A subgroup of intrahepatic cholangiocarcinoma and combined hepatocellular- cholangiocarcinoma contain a component of cholangiolocellular carcinoma , which is composed of small bile ductular cells . Ductular reaction , a reactive lesion at the portal tract interface comprising increased bile ductules , is frequently seen in chronic advanced liver diseases . Bile duct adenoma , a benign tumor /tumorous lesion is also composed of bile ductular cells . Differential diagnosis among these bile ductular tumors /lesions is sometimes difficult . Given overexpression of a polycomb group protein EZH 2 in intrahepatic cholangiocarcinoma and high expression of senescence-associated p 16 INK 4 a in ductular reactions , we plan to apply immunostaining for EZH 2 and p 16 INK 4 a for differential diagnosis of these bile ductular tumors /lesions . The expression of EZH 2 was seen in all cases of cholangiolocellular carcinomas , while it was not observed in bile duct adenomas or ductular reactions . In contrast , the expression of p 16 INK 4 a was seen in most bile duct adenomas and all ductular reactions , whereas it was barely seen in cholangiolocellular carcinomas . A borderline between cholangiolocellular carcinoma and the surrounding ductular reaction was clearly highlighted by the reverse expression pattern of EZH 2 and p 16 INK 4 a . In conclusion , immunostaining for EZH 2 and p 16 INK 4 a may be useful for differential diagnosis for bile ductular tumors /lesions .