血小板源性生长因子α受体D842V突变型胃肠间质瘤患者的临床病理特征及预后分析  

Clinicopathological features and prognosis of gastrointestinal stromal tumor with PDGFRA⁃D842V mutation

作　　者：李晓琦 屠霖[1] 汪明[1] 马欣俐 杨琳希 沈艳莹[2] 庄淳[1] 赵文毅[1] 邱江锋[1] 赵刚[1] 曹晖[1] Li Xiaoqi;Tu Lin;Wang Ming;Ma Xinli;Yang Linxi;Shen Yanying;Zhuang Chun;Zhao Wenyi;QiuJiangfeng;Zhao Gang;Cao Hui(Department of Gastrointestinal Surgery,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China;Department of Pathology,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属仁济医院胃肠外科,200127 [2]上海交通大学医学院附属仁济医院病理科,200127

出　　处：《中华胃肠外科杂志》2020年第9期872-879,共8页Chinese Journal of Gastrointestinal Surgery

基　　金：2017年上海市领军人才项目;国家自然科学基金青年科学基金项目(81702303)。

摘　　要：目的血小板源性生长因子α受体(PDGFRA)突变是胃肠间质瘤(GIST)中少见的一种突变类型,包括D842V位点在内的大多数PDGFRA第18外显子突变患者对伊马替尼具有高度耐药性,其治疗是临床的一大难点。本文探讨PDGFRA-D842V突变型GIST患者的临床病理特征、综合治疗效果及预后,以期为其临床治疗提供参考。方法采用回顾性队列研究方法,收集2005年1月至2020年5月间,在上海交通大学医学院附属仁济医院GIST诊疗中心接受诊治的71例PDGFRA突变型GIST患者的临床病理资料及随访资料,根据基因位点突变情况,将纳入患者分为D842V突变组(47例,66.2%)和非D842V突变组(24例,33.8%),比较D842V突变和非D842V两组患者的临床病理特征,并分析其疗效、复发和转移情况。结果D842V突变组男性28例,女性19例,中位年龄为60(36~82)岁;非D842V突变组男性16例,女性8例,中位年龄为62(30~81)岁。比较D842V突变组与非D842V突变组的年龄、性别、原发部位、手术方式、肿瘤最大径、核分裂象计数、CD117和DOG1表达情况、Ki-67增殖指数和危险度分级,差异均无统计学意义(均P>0.05)。D842V突变组和非D842V突变组CD34阳性率分别为89.4%(42/47)和62.5%(15/24),差异有统计学意义(χ^2=5.644,P=0.018)。D842V突变组和非D842V突变组中,未经术前治疗直接行R0切除者分别为44例和22例,因肿瘤破裂行急诊手术R1切除者各1例,经穿刺明确病理及突变类型后未行手术者各1例(其中1例D842V突变患者接受avapritinib治疗获得部分缓解),1例D842V突变患者因外院穿刺结果提示野生型GIST,术前接受了8个月的伊马替尼治疗后行R0切除。术后分别有5例D842V突变和5例非D842V突变的高危GIST患者接受了1年以上的伊马替尼术后辅助治疗。中位随访时间37(1~153)个月,D842V突变与非D842V突变患者的3年无病生存率分别为94.2%和100%(P=0.233)。单因素分析显示,核分裂象计数(P=0.002)、Ki-67增殖指Objective Platelet-derived growth factor alpha(PDGFRA)mutations are respectively rare in gastrointestinal stromal tumors(GIST).Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib.The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge.This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment,providing a reference for clinical practice.Methods A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020.According to the mutation site,the enrolled patients were divided into D842V mutation group and non-D842V mutation group.The differences of clinicopathologic characteristics between the two groups were compared.Furthermore,overall survival and prognostic factors were analyzed.Results A total of 71 patients with PDGFRA-mutant GIST were included in this study,including 47 cases of D842V mutation(66.2%)and 24 cases of non-D842V mutation(33.8%).There were 28 male patients and 19 female patients in D842V mutation group,with a median age of 60(36-82)years.There were 16 male patients and 8 female patients in non-D842V mutation group,with a median age of 62(30-81)years.There were no significant differences in age,gender,primary location,surgical procedure,tumor size,mitotic count,expression of CD117 and DOG1,Ki-67 proliferation index and modified NIH grade between the two groups(all P>0.05).The positive rate of CD34 was 89.4%(42/47)and 62.5%(15/24)in the D842V mutation group and the non-D842V mutation group,respectively,with a statistically significant difference(χ^2=5.644,P=0.018).Among all the cases,66 cases underwent R0 resection without preoperative treatment;two cases underwent emergency operation with R1 resection because of tumor rupture;2 cases were not operated after the pat

关 键 词：胃肠间质瘤 血小板源性生长因子受体α 临床病理特征 临床疗效 

分 类 号：R735[医药卫生—肿瘤]