KIT/PDGFRA基因“纯合性”突变胃肠间质瘤的临床病理特征及预后分析:一项多中心回顾性队列研究  

Clinicopathological features and prognosis of gastrointestinal stromal tumors with KIT/PDGFRA gene"homozygous mutation":a multicenter retrospective cohort study

作　　者：沈艳莹[1,7] 李晓琦 杨琳希 方勇 聂明明[4,7] 何子锐 侯英勇 曹晖[2,7] 汪明 沈坤堂 Shen Yanying;Li Xiaoqi;Yang Linxi;Fang Yong;Nie Mingming;He Zirui;Hou Yingyong;Cao Hui;Wang Ming;Shen Kuntang(Department of Pathology,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China;Department of Gastrointestinal Surgery,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China;Department of General Surgery,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of General Surgery,Changhai Hospital,Navy Medical University,Shanghai 200433,China;Department of General Surgery,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200025,China;Department of Pathology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Shanghai GIST Diagnosis and Treatment Cooperative Group)

机构地区：[1]上海交通大学医学院附属仁济医院病理科,200127 [2]上海交通大学医学院附属仁济医院胃肠外科,200127 [3]复旦大学附属中山医院普通外科,上海200032 [4]海军军医大学附属长海医院普通外科,上海200433 [5]上海交通大学医学院附属瑞金医院普通外科,200020 [6]复旦大学附属中山医院病理科,上海200032 [7]上海胃肠间质瘤诊疗协作组

出　　处：《中华胃肠外科杂志》2021年第9期804-813,共10页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金面上项目(82072669);国家自然科学基金青年项目(81702303);2017年上海市领军人才项目。

摘　　要：目的探讨具有KIT/PDGFRA基因“纯合性”突变胃肠间质瘤(GIST)患者的临床病理特征、靶向药物治疗效果及预后。方法采用回顾性队列研究和倾向性评分匹配方法。“纯合性”突变定义为应用一代测序法检测GIST的KIT/PDGFRA基因的状态时,表现为测序图中只有突变型基因序列,缺乏野生型序列或突变型基因序列的峰高远高于野生型基因序列(>3倍);“杂合性”突变定义为在测序图中表现为突变型基因序列与野生型基因序列同时存在,且峰高相近(≤3倍)。收集2008年1月至2021年5月上海4家医院[上海交通大学医学院附属仁济医院(70例)、复旦大学附属中山医院(14例)、海军军医大学附属长海医院(6例)、上海交通大学医学院附属瑞金医院(2例)]确诊为GIST并具有KIT/PDGFRA基因“纯合性”突变的92例患者的临床病理资料及随访信息。排除围手术期死亡、合并其他恶性肿瘤以及临床病理资料不完整的患者。观察分析患者的临床病理特征和靶向药物治疗效果,疗效评价采用Choi标准,分为肿瘤完全缓解(CR)、部分缓解(PR)、稳定病变(SD)和肿瘤进展(PD)。纳入同期经过手术完整切除的KIT基因11外显子“杂合性”突变高危GIST患者230例,以及应用伊马替尼(IM)治疗的复发或转移性“杂合性”KIT基因11外显子突变GIST病例117例,采用倾向评分匹配法,将KIT基因11外显子“杂合性”突变与“纯合性”突变的GIST患者组成1∶1配对进行生存分析,比较经手术完整切除的两组高危GIST患者的无病生存期(DFS),以及复发或转移性的两组GIST患者的无进展生存期(PFS)。结果在92例具有KIT/PDGFRA基因“纯合性”突变的GIST病例中,男性58例,女性34例,发病中位年龄62(31~91)岁;原发性GIST 83例。原发高危GIST(53例)、转移性GIST(21例)及复发性GIST(9例)占比90.2%(83/92)。KIT基因“纯合性”突变有90例(88例外显子11,1例外显子13,1例外显子1Objective To investigate the clinicopathological features of gastrointestinal stromal tumor(GIST)with KIT/PDGFRA"homozygous mutation",the efficacy of targeted therapy and the prognosis.Methods A retrospective cohort study and propensity score matching were used."Homozygous mutation"was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing,which showed that there was only mutant gene sequence in the sequencing map,lack of wild⁃type sequence or the peak height of mutant gene sequence was much higher than that of wild⁃type gene sequence(>3 times)."Heterozygous mutation"was defined as the mutant gene sequences coexisted with wild type gene sequences,and the peak height was similar(3 times or less).The clinicopathological data and follow⁃up information of 92 GIST patients with KIT/PDGFRA"homozygous mutation"were collected from 4 hospitals in Shanghai from January 2008 to May 2021(Renji Hospital,Shanghai Jiaotong University School of Medicine:70 cases;Zhongshan Hospital,Fudan University:14 cases;Changhai Hospital,Naval Military Medical University:6 cases and Ruijin Hospital,Shanghai Jiaotong University School of Medicine:2 cases).Patients with perioperative death,other malignancies,and incomplete clinicopathological information were excluded.The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed.The efficacy was evaluated using Choi criteria,which were divided into complete response(CR),partial response(PR),stable disease(SD)and progressive disease(PD).In addition,a total of 230 patients with high⁃risk GIST with"heterozygous mutation"in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with"heterozygous mutation"in exon 11 of KIT gene were included.The propensity score matching method was used to match GIST patients with"heterozygous"and"homozygous"mutations in exon 11 of KIT gene(1∶1)for survival analysis.The disease⁃free survival(DFS)between two groups of high⁃risk GIST patients who underwent co

关 键 词：胃肠间质瘤 KIT/PDGFRA基因 纯合性 临床病理特征 预后分析 

分 类 号：R735[医药卫生—肿瘤]