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

Lin LI; Liping Zhang; Yuchen Han; Weiya Wang; Yan Jin; Qingxin Xia; Yueping Liu; Jin Xiang; Chao Liu; Shanshan LU; Wei WU; Zhen Chen; Juan Pang; Yanfeng XI; Yushuang Zheng; Dongmei GU; Jun Fan; Xiaona Chang; Weiwei Wang; Liang Wang; Zhihong Zhang; Xiaochu Yan; Yi Sun; Ji LI; Feng Hou; Jingyuan Zhang; Rongfang Huang; Jianping LU; Zheng Wang; Yongbin HU; Hongtu Yuan; Yujie Dong; Lu Wang; Zhenyu KE; Jingshu Geng; Lei Guo; Jing Zhang; Jianming Ying

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

VernacularTitle: 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
Author: Lin LI ¹ ; Liping ZHANG ² ; Yuchen HAN ³ ; Weiya WANG ⁴ ; Yan JIN ^{5
,

6} ; Qingxin XIA ⁷ ; Yueping LIU ⁸ ; Jin XIANG ⁹ ; Chao LIU ¹⁰ ; Shanshan LU ¹¹ ; Wei WU ¹ ; Zhen CHEN ² ; Juan PANG ³ ; Yanfeng XI ⁴ ; Yushuang ZHENG ^{5
,

6} ; Dongmei GU ^{5
,

6} ; Jun FAN ⁷ ; Xiaona CHANG ⁷ ; Weiwei WANG ⁸ ; Liang WANG ⁹ ; Zhihong ZHANG ¹⁰ ; Xiaochu YAN ¹² ; Yi SUN ¹ ; Ji LI ² ; Feng HOU ³ ; Jingyuan ZHANG ⁴ ; Rongfang HUANG ^{5
,

6} ; Jianping LU ^{5
,

6} ; Zheng WANG ⁷ ; Yongbin HU ⁸ ; Hongtu YUAN ⁹ ; Yujie DONG ¹⁰ ; Lu WANG ¹³ ; Zhenyu KE ¹³ ; Jingshu GENG ¹ ; Lei GUO ¹ ; Jing ZHANG ¹ ; Jianming YING ¹
Author Information

1. 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
2. Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
3. Department of Pathology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China
4. Department of Pathology, West China Hospital of Sichuan University, Chengdu 610041, China
5. Department of Pathology, Fudan University Cancer Center
6. Department of Oncology, Shanghai Medical College of Fudan University, Shanghai 200032, China
7. Department of Molecular Pathology, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China
8. Department of Pathology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
9. 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
10. Department of Pathology, Guangdong Provincial People′s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
11. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
12. Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
13. Department of Pathology, Xijing Hospital, Air Force Military Medical University, Xi′an 710032, China
Collective Name:RATICAL (ALK testing in Chinese advanced non-small cell lung cancer patients: a national-wide multicenter prospective real world study) Research Group
Publication Type:Journal Article
Keywords: Lung neoplasms; Immunohistochemistry; Anaplastic lymphoma kinase
From: Chinese Journal of Pathology 2019;48(12):921-927
CountryChina
Language:Chinese
Abstract: 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.