MET扩增非小细胞肺癌患者的临床病理特征及其对克唑替尼的响应分析

The clinicopathological characteristics and response to crizotinib of non-small cell lung cancer patients with MET amplification

目的 探讨非小细胞肺癌患者MET基因扩增与临床病理特征的相关性,揭示MET扩增与其他驱动基因突变共存患者对克唑替尼的敏感性。方法 回顾性分析252例非小细胞肺癌患者的临床病理资料,采用二代测序法检测常见驱动基因EGFR、ALK、ROS1、RET、HER2、BRAF和MET的突变情况,特定突变患者采用Fish法进行验证;根据患者MET基因扩增情况进行分组,比较各组患者年龄、吸烟史、性别、病理类型、疾病阶段及其他驱动基因突变情况;收集MET扩增与其他驱动基因突变共存患者使用克唑替尼后的预后数据。结果 252例患者中,MET扩增发生率为19.4%(49/252),其中原发MET扩增和继发MET扩增突变率分别为16.2%(33/203)和31.2%(15/48)。MET扩增多见于Ⅲ~Ⅳ期肺癌(P=0.02)、骨转移(P=0.02)及ROS1融合阳性(P=0.02)患者,与年龄、性别、吸烟史、病理学分类无明显相关性(P>0.05)。31例MET扩增阳性患者具有其他驱动基因突变,其中5例患者使用克唑替尼进行治疗。5例使用克唑替尼的患者中,2例是原发MET扩增,3例是继发MET扩增;4例使用克唑替尼获得了较好的效果,1例死于重度感染。总结MET扩增在本研究人群中的突变率高于文献报道,且多见于临床分期较晚、骨转移、ROS1融合阳性患者。MET扩增与其他驱动基因突变共存的患者也能在一定程度上从克唑替尼中获益。

Objective To investigate the correlation between MET gene amplification and clinicopathological features in non-small cell lung cancer(NSCLC)patients,and to reveal the sensitivity to crizotinib of patients with coexistence of MET amplification and other driver gene mutations.Methods Retrospective data from 252 non-small cell lung cancer(NSCLC)patients were collected.Gene status of EGFR,ALK,ROS1,RET,HER2,BRAF,and MET were performed using second generation sequencing platform of HYK-PSTAR-IIA.In special MET amplification cases,MET were also validated by Fish method.Patients were divided into groups according to MET amplification detection results,and their age,smoking history,gender,pathological type,disease stage,and other driver gene mutations were compared among the groups.The prognostic data were also collected and analyzed of patients with coexisting MET amplification and other driver gene mutations after crizotinib treatment.Results Of the included 252 patients,49(19.4%)were positive for MET gene amplification.The fre-quency of de novo MET amplification and acquired MET amplification occurred in patients received EGFR-TKIs was 16.2%(33/203)and 31.2%(15/48),respectively.MET amplification was significantly associated with advanced stage(Ⅲ~Ⅳ)(P=0.02),bone metastases(P=0.02)and ROS1 fusion-positive(P=0.02).No significant differences in the age,history of smoking,sex,and pathologic types were found.Of the 31 patients who had coexistent MET amplification and other genetic alterations,five patients including two cases of de novo MET amplification and three cases of acquired MET amplification,were treated with crizotinib.Four patients achieved good response to crizotinib,and one patient died of severe infection.All patients achieved certain response.Conclusion The frequency of MET amplification in this study was higher than that was reported in the literature.We observed a trend towards a high prevalence of advanced stage,bone metastases,and ROS1 fu-sion-positive patients.Patients with the coexistence of MET amplification and other driver gene mutations could also have some benefits from crizotinib.