肺腺癌ALK Ventana-D5F3免疫组织化学检测结果判读一致性质控研究  

Consistency of ALK Ventana-D5F3 immunohistochemistry interpretation in lung adenocarcinoma among Chinese histopathologists

作　　者：李琳 张莉萍[2] 韩昱晨 王威亚[4] 金燕 夏庆欣 刘月平[7] 向锦[8] 刘超[9] 鲁姗姗 吴伟 陈振 庞娟 郗彦凤[14] 郑玉双[15] 顾冬梅[15] 范军 常晓娜 王伟伟 王亮[18] 张智弘[19] 阎晓初 孙意[21] 李霁[22] 侯峰[23] 张静渊[24] 黄榕芳[25] 卢建平[25] 王征[26] 胡永斌[27] 苑宏图 董宇杰[29] 王璐 克祯彧 耿敬姝[31] 郭蕾 张静 应建明 无 Li Lin;Zhang Liping;Han Yuchen;Wang Weiya;Jin Yan;Xia Qingxin;Liu Yueping;Xiang Jin;Liu Chao;Lu Shanshan;Wu Wei;Chen Zhen;Pang Juan;Xi Yanfeng;Zheng Yushuang;Gu Dongmei;Fan Jun;Chang Xiaona;Wang Weiwei;Wang Liang;Zhang Zhihong;Yan Xiaochu;Sun Yi;Li Ji;Hou Feng;Zhang Jingyuan;Huang Rongfang;Lu Jianping;Wang Zheng;Hu Yongbin;Yuan Hongtu;Dong Yujie;Wang Lu;Ke Zhenyu;Geng Jingshu;Guo Lei;Zhang Jing;Ying Jianming(Department of Pathology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Department of Pathology,Shanghai Pulmonary Hospital,School of Medicine,Tongji University,Shanghai 200433,China;Department of Pathology,Shanghai Chest Hospital,Shanghai Jiaotong Universitiy,Shanghai 200030,China;Department of Pathology,West China Hospital of Sichuan University,Chengdu 610041,China;Department of Pathology,Fudan University Cancer Center/Department of Oncology,Shanghai Medical College of Fudan University,Shanghai 200032,China;Department of Molecular Pathology,the Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450008,China;Department of Pathologyf the Fourth Hospital of Hebei Medical Universityf Shijiazhuang 050011,China;Department of Pathology,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Department of Pathology,Guangdong Provincial Peopled Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China;Department of Pathology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Pathology,Cancer Hospital of the University of Chinese Academy of Sciences,Hangzhou 310022,China;Department of Pathology,the First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310003,China;Department of Pathology,Tianjin Medical University Cancer Institute and Hospital,Tianjin 300060,China;Department of Pathology,Shanxi Cancer Hospital,Taiyuan 030013,Chi

机构地区：[1]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院病理科,100021 [2]同济大学附属上海市肺科医院病理科,200433 [3]上海市胸科医院上海交通大学附属胸科医院病理科,200030 [4]四川大学华西医院病理科,成都610041 [5]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,200032 [6]郑州大学附属肿瘤医院临床病理中心,450008 [7]河北医科大学第四医院病理科,石家庄050011 [8]华南肿瘤学国家重点实验室肿瘤医学协同创新中心中山大学肿瘤防治中心病理科,广州510060 [9]广东省人民医院广东省医学科学院病理科,广州510080 [10]复旦大学附属中山医院病理科,上海200032 [11]中国科学院大学附属肿瘤医院病理科,杭州310022 [12]浙江大学医学院附属第一医院病理科,杭州310003 [13]天津医科大学附属肿瘤医院病理科,300060 [14]山西省肿瘤医院病理科,太原030013 [15]苏州大学附属第一医院病理科,215006 [16]华中科技大学同济医学院附属协和医院病理科,武汉430022 [17]郑州大学第一附属医院病理科,450052 [18]中国医科大学附属第一医院病理科,沈阳110001 [19]南京医科大学第一附属医院病理科,210029 [20]陆军军医大学西南医院病理科,重庆400038 [21]中南大学湘雅二医院病理科,长沙410011 [22]中国医学科学院北京协和医学院北京协和医院病理科,100730 [23]青岛大学附属医院病理科,266003 [24]南京医科大学附属肿瘤医院江苏省肿瘤医院病理科,210009 [25]福建医科大学附属肿瘤医院病理科,福州350001 [26]北京医院病理科国家老年医学中心,100730 [27]中南大学湘雅医院病理科,长沙410008 [28]山东省肿瘤防治研究院病理科,济南250017 [29]首都医科大学附属北京胸科医院北京市结核病胸部肿瘤研究所病理科,101149 [30]空军军医大学西京医院病理科,西安710032 [31]哈尔滨医科大学附属肿�

出　　处：《中华病理学杂志》2019年第12期921-927,共7页Chinese Journal of Pathology

基　　金：北京市卫生与健康科技成果与适宜技术推广项目(2018-TG-58);中国癌症基金会项目(中国非小细胞肺癌生物标志物检测模式真实世界研究);中国医学科学院医学与健康科技创新工程项目(2017-I2M-2-003)。

摘　　要：目的 了解中国肺腺癌间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK) Ventana-D5F3免疫组织化学(IHC)检测在不同医院间病理医师判读结果的一致性,发现并解决真实世界中ALK IHC结果判读存在的问题,以期有效地指导ALK靶向药获益人群的准确筛选.方法 采用多中心回顾性研究,收集中国非小细胞肺癌ALK检测模式真实世界多中心研究组成员共31个中心于2018年1月至6月期间诊断为肺腺癌且行ALK Ventana-D5F3自动化IHC检测的病例共109例.采用Ventana iSCANcoreo数字病理切片扫描仪扫描成数字切片(200×).ALK IHC染色结果由各中心的高年资病理医师进行阅片,判读标准按产品说明书二元判读法(阳性、阴性)进行判读,并进行统计分析.判读不一致率最高的病例进行荧光原位杂交(FISH)、即时荧光定量聚合酶链反应(RT-PCR)、二代测序(NGS)检测.结果 所有IHC切片经专家组复阅确认,共有49例阳性病例和60例阴性病例,其中2例(编号2302和2701)原单位诊断为阳性但专家组确认为阴性的病例经FISH、RT-PCR、 NGS证实结果为阴性.对于此2例,医师的误判率(假阳性)分别为58.1%(18/31)和48.4%(15/31).仅有6位病理医师(6/31,19.4%)诊断准确率达100%.两两医师之间判读的一致性最低为75.8%.49例阳性病例中至少有1位医师判读为阴性者(假阴性)占26.5%(13/49),60例阴性病例中至少有1位医师判读为阳性者(假阳性)占41.7%(25/60),至少有1位专家判读为不确定者占31.2%(34/109).结论 真实世界中病理医师对ALK Vantana-D5F3 IHC检测结果的判读存在一定差异和误判,需要根据真实世界数据形成专家共识提供参考和指导.Objective To understand the consistency of ALK Ventana-D5F3 immunohistochemistry(IHC)interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals,and to recommend solution for the problems found during the interpretation of ALK IHC in real world,with the aim of the precise selection of patients who can benefit from ALK targeted therapy.Methods This was a multicenter and retrospective study.A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018.All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary(positive or negative)interpretation based on its manufacturer′s protocol.The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS.Results There were 49 ALK positive cases and 60 ALK negative cases,confirmed by re-evaluation by the specialist panel.Two cases(No.2302 and No.2701)scored as positive by local hospitals were rescored as negative,and were confirmed to be negative by RT-PCR/FISH/NGS.The false interpretation rate of these two cases was 58.1%(18/31)and 48.4%(15/31),respectively.Six out of 31(19.4%)pathologists got 100%accuracy.The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement(false negative)or positive judgement(false positive)in the 49 positive or 60 negative cases,accounted for 26.5%(13/49),41.7%(25/60),respectively,with at least one uncertainty interpretation accounted for 31.2%(34/109).Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test,which need to be guided by the oncoming expert consensus based on the real world data.

关 键 词：肺肿瘤 免疫组织化学 间变性淋巴瘤激酶 

分 类 号：R73[医药卫生—肿瘤]