The Overexpression of Enhancer of Zeste Homolog 2 (EZH2) May Be Related to Malignant Behaviors in Intraductal Papillary Neoplasm of the Bile Duct
Motoko Sasaki, Takashi Matsubara, Yasunori Sato, Norihide Yoneda, Yasuni Nakanuma. Kanazawa University Graduate School of Medicine, Kanazawa, Japan
Background: Intraductal papillary neoplasm of the bile duct (IPNB), which is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas, usually shows favorable prognosis, but occasionally is associated with invasive carcinoma. The overexpression of polycomb group protein enhancer of zeste homolog 2 (EZH2) is related to an epigenetic suppression of tumor suppressor genes, such as p16INK4a, and is reportedly involved in the progression of malignant tumours.
Design: We examined immunohistochemically the significance of EZH2 expression and its association with clinicopathological features, the expression of p16INK4a, MUC mucin core proteins (MUC1, MUC2, MUC5AC, MUC5B and MUC6) and p53 in perihilar IPNB with and without invasive carcinoma and extrahepatic IPNB. The subjects included 6 patients with cystic variant of IPNB (cystic type, M/F=3/3, 3 microinvasive and 3 non-invasive,), 6 with IPNB without invasive carcinoma (usual type, M/F=4/2), 11 with IPNB associated with invasive carcinoma (invasive type, M/F=6/5) and 6 with extrahepatic IPNB (ExH-type, all invasive, M/F=5/1). Mucinous cystic neoplasms with ovarian-like stroma were excluded.
Results: The expression of EZH2 was low (labeling index; LI <20%) in all cystic and usual types, whereas it was significantly high in invasive and ExH types (p<0.05). The expression of EZH2 was significantly associated with tumor invasion in IPNB (p<0.01). The expression of p16 INK4a was high (LI >20%) in 3 cystic types (50%), 2 invasive types (18%) and 2 ExH-types (33%). The expression of EZH2 was inversely correlated with the expression of p16INK4a (p<0.05). The expression of MUC1 was significantly associated with the degree of tumor invasion in IPNB (p<0.05). The expression of MUC2 was more evident in invasive type, especially those associated with mucinous carcinoma (p<0.05 versus cystic and usual type). The expression of MUC5AC and MUC5B is evident in all types of IPNB. The expression of MUC6 was significantly more evident in cystic and usual types, compared to ExH type (p<0.05). p53 expression was negative (<5%) in all cystic and usual types, whereas p53 expression was higher level in invasive and ExH types (p<0.05). The expression of EZH2 was significantly correlated with the expression of MUC1 (p<0.01) and inversely correlated with the expression of MUC6 (p<0.05).
Conclusions: The over-expression of EZH2 may be related to an upregulation of MUC1 expression and a downregulation of MUC6 expression and may be associated with malignant behaviors in IPNB.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 237, Tuesday Afternoon