关键词: 肉瘤样肝细胞癌, MET, 基因扩增, 预后, 靶向治疗

Abstract:  Background and purpose: Sarcomatoid hepatocellular carcinoma (SHC) is a rare and aggressive neoplasm of the liver. MET gene aberrations have emerged as important prognostic biomarkers for tumors, and MET-targeted inhibitor has become an important direction in the treatment of advanced tumors. The status of MET gene amplification in the SHC tissues remains unclear. The aim of this study was to investigate the correlations between MET gene amplification and the clinicopathological factors in patients with SHC and its prognostic values. Methods: Twenty-two patients with SHC were identified from the liver resection pathology files in the database of Zhongshan Hospital, Fudan University from Jan. 2008 to Dec. 2016. MET gene amplification was analyzed by fluorescence in situ hybridization (FISH), followed by subsequent clinicopathological correlative studies. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). The log-rank test was applied to compare survival curves. Multivariate COX regression models were used for prognostic analysis. Results: MET gene amplification was observed in 5 patients (22.7%), and MET FISH positive cells mainly located in the sarcomatoid area of the tumor (4 cases). Patients with MET gene amplification and incomplete tumor capsule had significantly shorter median OS (6.8 months vs 24.0 months, 8.5 months vs 41.3 months, P=0.001 and 0.001) compared with those who did not. Patients with a solitary tumor and China Liver Cancer Staging (CNLC) stage Ⅰ disease had significantly favorable DFS (10.4 months vs 3.8 months, 10.4 months vs 3.8 months, P=0.027 and 0.017) than the patients with multiple tumors and CNLC stage Ⅱ+Ⅲ+Ⅳ diseases. The results of the multivariate COX proportional hazards model revealed MET gene amplification as an independent prognostic factor for mortality. Conclusion: SHC tissue has a high rate of MET gene amplification, which is an independent predictor of poor prognosis in patients with SHC. This study may provide a new strategy and clinical basis for the treatment of this rare tumor.

Key words: Sarcomatoid hepatocellular carcinoma, MET, Gene amplification, Prognosis, Targeted therapy