Abstract 2277: Prognostic impact of enhancer of zeste homologue 2 (EZH2) in patients underwent hepatectomy for colorectal liver metastases who received preoperative oxaliplatin-based chemotherapy

Purpose: Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the third leading cause of cancer mortality in Japan. Almost 15% and 10% of patients with CRC are diagnosed with synchronous and metachronous liver metastasis, respectively. In the last decade, the therapeutic strategies including chemotherapy and molecular targeted therapy have improved. However, the prognosis of patients with CRC remains poor because of their acquirement of chemoresistance. Previous studies have shown that enhancer of zeste homologue 2 (EZH2) is associated with proliferation of various cancers. EZH2 is the catalytic subunit of Polycomb repressive complex2 (PRC2) which catalyzes the methylation of lysine 27 on histone H3 (H3K27), leading to repress the transcription of tumor-suppressor genes. In addition, high EZH2 expression is associated with the resistance to cisplatin in non-small cell lung carcinoma. However, the association between the resistance to oxaliplatin and the expression of EZH2 is unrevealed. The aim of this study is to investigate the correlation between the expression of EZH2 and response to oxaliplatin-based chemotherapy as well as survival of patients with colorectal liver metastasis (CRLM). Experimental Design: Sixty-one patients who underwent first-line oxaliplatin-based chemotherapy before resection of CRLM were enrolled in this study. Immunohistochemistry of EZH2 was performed, and then the correlation between response to chemotherapy and survival was evaluated. Results: Immunohistochemistry revealed 38 patients (62.3%) with high EZH2 expression, and 23 patients (37.7%) with low EZH2 expression. Of the 38 patients with EZH2 high expression, 15 patients (39.5%) responded to oxaliplatin-based chemotherapy with either complete response or partial response. Of the 23 patients with low EZH2 expression, 14 patients (60.9%) exhibited a response to chemotherapy. There was significant difference in response to oxaliplatin-based chemotherapy between high and low EZH2 expression patients (p = 0.04). Univariate survival analysis indicated that patients with high EZH2 expression had a lower overall survival than those with low EZH2 expression. Moreover, multivariate Cox regression analysis revealed that high EZH2 expression was an independent prognostic factor for overall survival. Kaplan-Meier survival curves also confirmed that high EZH2 expression correlates with poor prognosis in patients who underwent hepatectomy for CRLM. Conclusions: Our results indicated that prognosis of patients with high EZH2 expression who received preoperative oxaliplatin-based chemotherapy and underwent hepatectomy for CRLM was worse than those with low EZH2 expression. EZH2 may be a predictive factor for oxaliplatin-based chemotherapy response and overall survival in patients with CRLM. Citation Format: Mayuko Ohuchi, Yasuo Sakamoto, Ryuma Tokunaga, Kenichi Nakamura, Yuki Kiyozumi, Daisuke Izumi, Keisuke Kosumi, Kazuto Harada, Junji Kurashige, Yukiharu Hiyoshi, Shiro Iwagami, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. Prognostic impact of enhancer of zeste homologue 2 (EZH2) in patients underwent hepatectomy for colorectal liver metastases who received preoperative oxaliplatin-based chemotherapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2277. doi:10.1158/1538-7445.AM2015-2277