Abstract 4732: Vasohibine-1 negative and EZH2 positive may predict the prognosis of cholangiocarcinoma

Abstract

Abstract Background: Vasohibin-1 (VASH1) is isolated as an endogenous angiogenesis inhibitor produced by the vascular endothelium, and the status of VASH1 expression has been documented in various cancer prognosis. Some reports shows that VASH1 was negatively regulated by enhancer of zeste homolog 2 (EZH2) epigenetically. The aim of this study was to assess the relationship between EZH2 and VASH1, and the prognostic value of this two molecules in intrahepatic cholangiocarcinoma (ICC) patients. Method: We examine 47 cases of intrahepatic cholangiocarcinoma to which the R0 liver resection had been performed by our department between 1993 years and 2010. Immunohistochemical staining of VASH1 and EZH2 was performed using paraffin-embedded block, and we examined the relation among the expression of VASH1 and a clinicopathological factor (sex, age, tumor diameter, tumor number, differentiation level, microscopic vascular invasion, and metastasis in lymph node), EZH2 expression, recurrence-free survival (RFS) and overall survival (OS). Result: VASH1 and EZH2 positivity was observed in 24 (51.1%) and 24 (51.1%) patients respectively, and VASH1 positivity was inversely correlated with EZH2 high expression (R=0.3870, p=0.0018). VASH1 positivity was not significantly correlate with RFS or OS. On the other hands, VASH1 negative and EZH2 positive was observed in 17 (36.2%) patients, and was a significant disadvantage to both RFS (relative risk (RR) 3.39, 95% confidence interval (CI) 1.28-8.67, p=0.0157) and OS (RR 3.69, 95% CI 1.20-11.2, 0.0237) in univariate Cox hazard analysis. In multivariate analysis, VASH1 negative and EZH2 positive group was an independent risk factor for both RFS (RR 4.19, 95% CI 1.33-13.13, p=0.0150), and OS (RR 8.11, 95% CI 2.01-42.1, p=0.0030). Conclusion: The expression of VASH1 was inversely correlate with EZH2 expression. VASH1 negative and EZH2 positive was an independent risk factor for OS and DFS in ICC patients. Citation Format: Shigeki Nakagawa, Yasuo Sakamoto, Ryuma Tokunaga, Takaaki Higashi, Keita Sakamoto, Akira Chikamoto, Takatoshi Ishiko, Toru Beppu, Hideo Baba. Vasohibine-1 negative and EZH2 positive may predict the prognosis of cholangiocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4732. doi:10.1158/1538-7445.AM2014-4732