中国癌症杂志 ›› 2020, Vol. 30 ›› Issue (9): 641-649.doi: 10.19401/j.cnki.1007-3639.2020.09.001

• 论著 • 上一篇    下一篇

肉瘤样肝细胞癌中MET基因扩增与预后的相关性分析

张 欣 1 ,周 成 2 ,周恺乾 2 ,柏乾明 3 ,蒋冬先 1 ,宿杰阿克苏 1 ,侯英勇 1 ,王 征 2 ,纪 元 1   

  1. 1. 复旦大学附属中山医院病理科,上海 200032 ;
    2. 复旦大学附属中山医院肝外科,上海 200032 ;
    3. 复旦大学附属肿瘤医院病理科,复旦大学上海医学院肿瘤学系,上海 200032
  • 出版日期:2020-09-30 发布日期:2020-10-10
  • 通信作者: 纪 元 E-mail: ji.yuan@zs-hospital.sh.cn
  • 基金资助:
    国家自然科学基金(81400645);上海市临床重点专科项目(shslczdzk01302)。

MET gene amplification and its prognostic role in sarcomatoid hepatocellular carcinoma

ZHANG Xin 1 , ZHOU Cheng 2 , ZHOU Kaiqian 2 , BAI Qianming 3 , JIANG Dongxian 1 , SUJIE Akesu 1 , HOU Yingyong 1 , WANG Zheng 2 , JI Yuan 1   

  1. 1. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; 2. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; 3. Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Online:2020-09-30 Published:2020-10-10
  • Contact: JI Yuan E-mail: ji.yuan@zs-hospital.sh.cn

摘要: 背景与目的:肉瘤样肝细胞癌(sarcomatoid hepatocellular carcinoma,SHC)是一种罕见且高度恶性的肝脏肿瘤。MET基因异常具有肿瘤预后预测价值,以MET为靶点的抑制剂已成为晚期肿瘤治疗的重要方向,然而SHC组织中MET基因扩增状态尚不明确。探讨SHC中MET基因扩增与临床病理学因素的相关性及其预后预测价值。方法:收集2008年1月—2016年12月于复旦大学附属中山医院经病理学检查确诊的22例SHC患者资料。采用荧光原位杂交(fluorescence in situ hybridization,FISH)法检测上述患者的MET基因扩增情况,并结合临床病理学资料进行统计学分析。采用Kaplan-Meier模型分析总生存期(overall survival,OS)及无病生存期(disease-free survival,DFS),采用log-rank检验比较生存曲线,采用多因素COX回归模型分析SHC中独立的预后因素。结果:22例SHC患者中,MET基因扩增5例(22.7%)。MET基因扩增存在异质性,主要位于分化差的梭形细胞区域(4例)。MET基因扩增的SHC患者中位OS明显短于MET阴性患者(6.8个月 vs 24.0个月,P=0.001)。SHC中具有完整肿瘤包膜的患者中位OS明显长于包膜不完整的患者(41.3个月 vs 8.5个月,P=0.001)。单灶肿瘤及中国肝癌分期(China Liver Cancer Staging,CNLC)Ⅰ期患者的中位DFS较多灶肿瘤及Ⅱ+Ⅲ+Ⅳ期患者明显延长(10.4个月 vs 3.8个月,12.4个月 vs 3.8个月,P=0.027和0.017)。MET基因扩增是SHC独立的预后因子。论:22.7%(5/22)的SHC中存在MET基因扩增。MET基因扩增的SHC患者预后更差,是其预后的独立危险因素。该研究结果为该罕见肿瘤的治疗提供了新策略和临床依据。

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