Jia Fan¹, Huichuan Sun¹, Xiaodong Zhu¹, Hui Zhou², Xiaojun Huang², Zhiqiang Du², Yanni Zhang²

¹Liver Cancer Institute, Zhongshan Hospital, Fudan University, ²Amgen China R&D Center, Shanghai

Objective:MET is a potential therapeutic target in hepatocellular carcinoma (HCC). This study evaluated MET expression and amplification in Chinese HCC patients and investigated the relationship with clinical outcomes. Method: Resection tumor samples from HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage C were retrospectively assessed for MET protein levels by immunohistochemistry (IHC; Dako) and MET gene copy numbers by fluorescence in situ hybridization (FISH; Dako). MET-positive: membrane protein staining in ≥25% tumor cells (25%cut-off), or intermediate (2+) or strong (3+) staining of the membrane (2+/3+). MET-amplified: MET to centromere ratio ≥2.0. Tests for the association between Kaplan-Meier RFS, OS and MET status (log-rank test) and clinical parameters (Fisher's exact), and the association between MET expression and amplification (Pearson Correlation) conducted. Result: A total of 264 eligible patients provided IHC samples; 88 (33.3%) and 86 cases (32.6%) showed high MET expression with definitions of 25% cutoff and 2+/3+, respectively. Of 265 patients with valid FISH results, the MET amplification rate was 9.1%. Liver cirrhosis status was associated with MET amplification (P=0.018) but not MET expression. Borderline significant OS and RFS difference was identified when high MET expression was defined as IHC 2+ or 3+, detailed RFS and OS data by MET status are shown (table). In 258 of patient samples, MET high expression with strong staining (3+) was associated with MET gene copy number (r=0.63). Conclusion:Borderline significant difference was found when high MET expression was defined as IHC 2+or 3+. A larger prospective analysis of the potential prognostic role of MET in HCC patients is needed. RFS OS MET high expression 25% cut-off (MET high vs. MET low) 5.85 vs. 6.53 months (P=0.76) 13.1 vs. 11.5 months (P=0.74) IHC 2+/3+ (MET high vs. MET low) 5.03 vs. 6.73 months (P=0.06) 10.5 vs. 13.9 months (P=0.076) MET amplification MET/centromere ratio≥2.0 (MET amplified vs. non-amplified) 5.13 vs. 6.3 months (P=0.69) 14 vs. 11.5 months (P=0.95).

Key Words: MET  HCC