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.
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。.
Keywords: Anaplastic lymphoma kinase; Immunohistochemistry; Lung neoplasms.