Abstract 1055: Enhancer of Zeste Homologue 2 (EZH2) may relate to progression of intra and extrahepatic cholangiocarcinoma

Abstract

Abstract [Background and Aims]Enhancer of Zeste Homolog 2 (EZH2) is one of the polycomb proteins and involved in the progress of several solid tumors by methylating histone3 Lysin27 (H3K27) and silencing various genes. However, the role of EZH2 in cholangiocarcinoma has not been clarified. In this study, we investigated the significance of EZH2 expression in intrahepatic and extrahepatic cholangiocarcinoma progression.[Patients and Methods]Fourty-seven intrahepatic cholangiocarcinoma (ICC) patients and 45 extrahepatic cholangiocarcinoma (ECC) patients treated with curative resection from 1993 to 2010 were enrolled. We examined the EZH2 expression by immunohistochemistry, and relationship between EZH2 expression and clinicopathological factors, such as gender, age, CA19-9, tumor diameter, tumor number, histological vascular invasion, differentiation, lymph node metastasis and prognosis. To assess whether EZH2 relates to angiogenesis and tumor growth, Ki67 expression and microvessel density (MVD) using CD34 were also examined by immunohistochemistry. EZH2 expression was investigated eight cholangiocarcinoma cell lines. Using small interfering RNA against EZH2, the influence of EZH2 knock-down on cholangiocarcinoma cell proliferation and invasion was studied in vitro. [Results]In ICC, 24 patients (51.0%) shows a high expression of EZH2 when the cutoff value was determined to be 10%. The EZH2 high expression is significantly correlated with tumor diameter > 3.5cm (P=0.0113) and MVD score (P=0.039). The high EZH2 expression group showed significantly worse overall survival (p=0.045). In ECC, 19 patients(42.2%) showed a high EZH2 expression. The EZH2 high expression is significantly correlated with positive lymph node metastasis (p=0.0469), high Ki67 expression (P=0.0017). The high EZH2 expression group showed significantly worse overall survival (P=0.0261). All of the eight cholangiocarcinoma cell lines expressed EZH2 in a various level. When we knock down the expression of EZH2 in RBE cells, the expression of H3K27 was reduced and cell growth decreased. However, EZH2 down-regulation didn't affect cell invasion.[Conclusion]EZH2 may relate to the progression of intra and extrahepatic cholangiocarcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1055. doi:1538-7445.AM2012-1055