Intrahepatic cholangiocarcinoma arising in chronic advanced
liver disease sometimes contains a component of cholangiolocellular
carcinoma.
Bile duct adenoma, a benign
tumor/tumorous lesion and ductular reaction, is also composed of bile ductular cells, and the differential diagnosis is sometimes difficult. We have previously reported that cholangiolocellular
carcinoma showed overexpression of a
polycomb group protein EZH2, which participates in bypass/escape from cellular senescence during
carcinogenesis. In contrast, the ductular reaction showed high expression of senescence-associated
p16(INK4a). In this study, we examined whether immunostaining for EZH2 and
p16(INK4a) is useful for differential diagnosis among cholangiolocellular
carcinoma,
bile duct adenoma, and ductular reactions. Subjects included 33 patients with
intrahepatic cholangiocarcinoma and combined hepatocellular-
cholangiocarcinoma with components of cholangiolocellular
carcinoma and 16 patients with
bile duct adenoma. The expressions of EZH2 and
p16(INK4a) were examined immunohistochemically. The expression of EZH2 was seen in all cases of cholangiolocellular
carcinomas, but it was not observed in
bile duct adenomas and ductular reactions, which were seen around
carcinomas in 80% of cases. The extensive expression of
p16(INK4a) was seen only in 4 cases of cholangiolocellular
carcinomas (12%). In contrast, the expression of
p16(INK4a) was seen in 13 cases (81%) of
bile duct adenomas and in all cases of ductular reactions. The borderline between the component of cholangiolocellular
carcinoma and the surrounding ductular reaction was clearly highlighted by the reverse expression pattern of EZH2 and
p16(INK4a) in 69% of cases. In conclusion, immunostaining for EZH2 and
p16(INK4a) may be useful for differential diagnosis among cholangiolocellular
carcinomas,
bile duct adenomas, and ductular reactions.