Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Am J Surg Pathol. 2014 Mar;38(3):364-9. doi: 10.1097/PAS.0000000000000125.
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.
在慢性进展性肝病中发生的肝内胆管细胞癌有时包含胆管细胞癌成分。胆管腺瘤是一种良性肿瘤/瘤样病变和胆管反应，也是由胆管细胞组成的，因此鉴别诊断有时较为困难。我们之前报道过，胆管细胞癌中多梳蛋白组蛋白 EZH2 表达过度，该蛋白参与致癌过程中细胞衰老的旁路/逃逸。相比之下，胆管反应中衰老相关的 p16(INK4a)表达较高。在这项研究中，我们研究了免疫组化检测 EZH2 和 p16(INK4a)是否有助于胆管细胞癌、胆管腺瘤和胆管反应的鉴别诊断。研究对象包括 33 例具有胆管细胞癌成分的肝内胆管癌和混合性肝细胞-胆管细胞癌患者和 16 例胆管腺瘤患者。通过免疫组化检测 EZH2 和 p16(INK4a)的表达。所有胆管细胞癌病例均可见 EZH2 的表达，但胆管腺瘤和胆管反应均未见 EZH2 表达，胆管反应在 80%的癌旁病例中可见。广泛的 p16(INK4a)表达仅见于 4 例胆管细胞癌（12%）。相比之下，13 例（81%）胆管腺瘤和所有胆管反应均可见 p16(INK4a)表达。在 69%的病例中，EZH2 和 p16(INK4a)表达模式的逆转清楚地突出了胆管细胞癌成分与周围胆管反应之间的界限。综上所述，免疫组化检测 EZH2 和 p16(INK4a)可能有助于胆管细胞癌、胆管腺瘤和胆管反应的鉴别诊断。
