非小细胞肺癌PD-L1免疫组织化学检测规范中国专家共识
中国肺癌杂志2020 年9 月第23 卷第9 期 Chin J Lung Cancer, September 2020, Vol.23, No.9
DOI: 10.3779/j.issn.1009-3419.2020.101.43
中国抗癌协会肿瘤病理专业委员会肺癌学组,中国抗癌协会肺癌专业委员会,PD-L1检测共识专家组
Chinese Expert Consensus on Standards of PD-L1 Immunohistochemistry Testing for Non-small Cell Lung Cancer
Corresponding author: Dongmei LIN, E-mail: lindm3@bjmu.edu.cn;
Shun LU, E-mail: shunlu@sjtu.edu.cn
1 引言
近年来,以程序性死亡受体1(programmed death-1, PD-1)/PD配体1(PD ligand 1, PD-L1)免疫检查点抑制剂为主的免疫治疗在晚期肺癌中取得了突破性的进展,改变了该领域的治疗格局,为患者带来了更多生存获益。虽然对于免疫治疗适宜人群筛选和疗效预测的生物标志物越来越多,但PD-L1仍是目前应用最为广泛的指标。免疫组织化学
随着PD-1/PD-L1免疫检查点抑制剂临床试验及应用的广泛开展,大量相关药物批准上市,分别获得美国食品药品监督管理局(Food and Drug Administration, FDA)、欧盟(European Communities, CE)认证和国家药品监督管理局(National Medical Products Administration, NMPA) 的批准。按照《中国非小细胞肺癌免疫检查点抑制剂治疗专家共识(2019版)》 [1] 内容推荐,目前针对晚期NSCLC 驱动基因阴性患者,中国已有多个PD-1/PD-L1抑制剂适用于一线、二线或以上治疗[2],其中PD-L1检测结果可以作为伴随诊断指导晚期NSCLC患者一线接受帕博利珠单抗单药或联合治疗。PD -L1检测结果也可作为补充诊断为晚期NSCLC患者接受纳武利尤单抗作为二线或以上治疗提供信息。
3 免疫检查点抑制剂预测标记物PD-L1指标使用
随着PD-1/PD-L1免疫检查点抑制剂获批,NSCLC患者PD-L1免疫组化检测试剂等也随适应证需要作为伴随诊 断或补充诊断而相应获批[3,4]。其中最大特点是各个药物分别对应不同的PD-L1试剂克隆或平台,且其判读阈值也各 不相同[5]。表1汇总了FDA、CE认证和NMPA对NSCLC患者 免疫治疗时所需使用PD-L1检测试剂和检测平台的获批情 况(截止2020年5月31日)。本共识建议选择我国NMPA批 准的免疫组化检测试剂盒或抗体试剂,具体推荐内容详见表1 。
表 1 不同国家地区NSCLC患者PD-L1检测试剂和检测平台获批情况
Tab 1 Approval status of PD-L1 assays and platforms in selected countries/region
试剂名称 |
抗体克隆号 |
检测平台 |
药物通用名 |
FDA 及获批阈值 |
CE认证 及获批阈值 |
NMPA 及获批阈值 |
推荐级别 |
PD-L1 IHC 22C3 |
22C3 |
Dako Autostainer |
帕博利珠单抗 |
伴随诊断 |
认证 |
批准 |
优先 |
pharmDx |
鼠单克隆一抗 |
Link48 |
|
TPS≥1% |
TPS≥1%、TPS≥50% |
TPS≥1% |
推荐 |
22C3抗体试剂 |
22C3 鼠单克隆一抗 |
Dako Autostainer Link48 |
帕博利珠单抗 |
/ |
/ |
批准TPS≥1% |
优先推荐(需 LDT确认) |
PD-L1 IHC 28-8 |
28-8 |
Dako Autostainer |
纳武利尤单抗 |
补充诊断(非鳞状 |
认证(非鳞状 |
批准 |
推荐 |
pharmDx |
兔单克隆一抗 |
Link48 |
|
NSCLC) TC≥1%、TC≥5%、TC≥10% 伴随诊断(NSCLC) TC≥1%(纳武利尤单抗联合伊匹单抗) |
NSCLC) TC≥1%、TC≥ 5%、TC≥10% |
(非鳞状NSCLC) TC≥1% |
|
VENTANA PD-L1 (SP142) assay |
SP142 兔单克隆一抗 |
Ventana BenchMark ULTRA |
阿替利珠单抗 |
补充诊断/伴随诊断 TC≥50%或IC≥ 10% |
认证 TC≥50%或IC≥ 10% TC≥1%或IC≥1% |
/ |
可考虑 |
VENTANA PD-L1 (SP263) assay |
SP263 兔单克隆一抗 |
Ventana BenchMark ULTRA |
纳武利尤单抗 |
/ |
认证 TC≥1%、≥5%、 ≥10% |
/ |
可考虑 |
|
|
|
帕博利珠单抗 |
|
认证 TC≥50%——一 线治疗 TC≥1%——二线治疗 |
|
|
|
|
|
度伐利尤单抗 |
|
认证,TC≥1% |
|
|
“/”代表未获批;TPS:肿瘤比例评分;TC:肿瘤细胞;IC:免疫细胞;LDT:实验室自建检测;FDA:美国食品药品监督管理局;CE:欧盟;NMPA:国家药品监督管理局。PD-L1: programmed cell death-ligand 1. NSCLC: non-small cell lung cancer.
除PD-L1(22C3)试剂盒获批以外,其浓缩液也于2020 年5月获NMPA批准作为体外诊断试剂,用于实验室自建检测(laboratory developed tests, LDT)。根据各自实验室性能确认结果,PD-L1浓缩抗体经相应比例预稀释后,于相应的 免疫组化染色机(Dako Autostainer Link48)染色,其判读结果可作为PD-L1伴随诊断,以指导临床评估是否可使用 帕博利珠单抗治疗NSCLC患者,如果判读结果TPS≥1%, 则认为该样本存在PD-L1阳性表达结果。
PD-L1免疫组化检测的获批试剂对应药物各有不同[1,4,6-8],因此各检测平台和试剂间的相关性和一致性也是临床医生与病理医生关注的重点。PD-L1检测抗体在NSCLC中相关性和一致性的研究至今已有很多,其中比较有影响力的是由国际肺癌研究协会(I nternational Association for Study of Lung Cancer, IASLC)牵头进行的蓝印计划(The Blueprint Project)I和II[9,10]。研究对比了克隆号28-8、22C3、SP263、SP142及73-10(蓝印计划研究II期) 这4种-5种检测抗体,结果显示:①28-8、22C3、SP263对 肿瘤细胞染色的阳性百分比相似,一致性较高;②SP142对 肿瘤细胞染色的灵敏度较低,与其他抗体间的一致性低;
③73-10相比于其他抗体表现出更强的敏感性。④病理学家对PD-L1在肿瘤细胞中表达分数评估一致性较高,而对 免疫细胞PD-L1表达结果评估一致性较差。国内也开展了一些关于PD-L1检测抗体相关性和一致性的研究[11],结果与国际报道一致,显示22C3、28-8和SP263对肿瘤细胞染色一致性较高(ρ=0.729-0.809),SP142的肿瘤细胞着色较 弱,灵敏度较低。不过此类研究目前仅局限于分析验证领域,尚缺乏不同检测抗体间一致性的临床疗效验证。
4.2 PD-L1检测时机 PD-L1的检测结果可以指导一线用药,因此推荐在晚期NSCLC患者初诊时进行PD-L1免疫 组化检测。《2019版中国非小细胞肺癌免疫检查点抑制剂治疗专家共识》[1]和《2019版中国临床肿瘤学会(CSCO) 原发性肺癌诊疗指南》[16]提出,基于K EYNOTE-024[17,18] 和KEYNOTE-042[19]研究的结果,帕博利珠单抗单药作为 一线治疗时,需要检测患者的PD-L1表达,且与美国国立 综合癌症网络(National Comprehensive Cancer Network, NCCN)NSCLC临床实践指南[20]推荐内容一致,将PD-L1 检测与表皮生长因子受体(epidermal growth factor receptor, EGFR)、间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)等基因检测列入同等地位。当PD-1/PD-L1抑制剂与 含铂双药联合用于一线治疗或用于后线治疗时,PD-L1表 达的检测并非强制,但该检测可能会提供有用的信息[16]。因此,晚期NSCLC患者确诊后进行PD-L1免疫组化检测和 驱动基因检测同等重要。
5.1 PD-L1检测标本要求 检测标本选择是有效评估肿瘤组织PD-L1表达的关键步骤。影响该领域临床实践的问题集 中于标本类型与判读标准等方面。
各检测试剂盒名称、平台、检测细胞类型、判读阈值等信息请参见表1。使用各PD-L1克隆号抗体检测NSCLC判读注 意事项具体如下。
5.3 检测的规范化报告模式推荐 PD-L1 IHC检测的结果报告中除了常规病理报告中的基本信息外,还应包括标本信
5.5 检测质控 无论选择何种PD-L1免疫组化检测试剂及平台,都需要行之有效的质量控制体系。其中,实验室内部质控是确保PD-L1免疫组化检测质量的关键,也是实验室外 部质评的前提。
5.5.2 实验室外部质评 参与室间质评活动是实验室外部质评的主要方式。实验室应定期参加PD-L1检测室间质评活动,每年至少2次。室间质评可通过参加国内权威机构举办的室间质评活动来完成,也可通过与其他实验室(如已获得资格认可的实验室、使用相同检测方法的实验室等)比对的方式确定检测结果的可信度。
肿瘤细胞 PD-L1 表达水平:______% (TPS/TC)免疫细胞 PD-L1 表达水平: % (IC)
备注:本检测结果仅为临床提供参考,请结合临床情况与试剂要求用药。
图 1 PD-L1检测报告模板示意Fig 1 PD-L1 test report template
尽管PD-L1表达对PD-1/PD-L1免疫检查点抑制剂的 疗效预测作用已经获得国内外监管机构的一致认可,但在研究及临床应用中仍有一些与PD-L1表达相关的科学问题需要进一步探讨。
(条)的检测数值,或许更加接近肿瘤本身PD-L1的表达状 况。当然相关临床实践问题需待进一步研究不断充实并完善。
PD-1表达是动态变化的,但由于现有研究样本量有限,临床试验入组标准不统一,目前各个研究的结论存在一定不一致之处,对此仍有待进一步探索研究。因此,目前建议临床实践中尽可能使用免疫治疗前最近期的标本进行PD-L1检测,若近期标本不可及,可考虑采用3年内的组织/细胞蜡块标本。
PD-L1检测作为预测PD-1/PD-L1免疫检查点抑制剂用 于晚期NSCLC一线、二线及以上治疗的疗效预测生物标志物,已在绝大多数病理实验室中得以应用,并被临床医生广泛应用于筛选或辅助判断免疫治疗中可能获益的患者。规范化操作程序和标准化结果判读能提高PD-L1检测的准确性和可重复性。另外,加强临床与病理的沟通交流将有助于获取更准确的PD-L1检测结果及对治疗疗效的客 观评价。本共识后续将根据临床诊治进展及临床实践不断完善,进一步更新。
中国非小细胞肺癌免疫检查点抑制剂治疗专家共识(2019年版).
中国肺癌杂志, 2020, 23(2): 65-76.] doi: 10.3779/j.issn.1009-3419.202
2 National Medical Products Administration (Data query), Available at: http://app1.nmpa.gov.cn/datasearchcnda/face3/dir.html?type=yp
3 List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools), Available at: https://www.fda.gov/medical- devices/vitro-diagnostics/list-cleared-or-approved-companion- diagnostic-devices-vitro-and-imaging-tools
4 Notification of import approval on 13 May 2020, Available at: http:// www.nmpa.gov.cn/WS04/CL2470/377383.html
5 Lantuejoul S, Sound-Tsao M, Cooper WA, et al. PD-L1 testing for lung cancer in 2019: perspective from the IASLC pathology committee. J Thorac Oncol, 2020, 15(4): 499-519. doi: 10.1016/j.jtho.2019.12.107
6 Premarket Approval (PMA), Available at: https://www.accessdata.fda. gov/scripts/cdrh/cfdocs/cf PMA/pma.cfm
7 VENTANA PD-L1 (SP263) Assay (CE IVD), Available at: https:// diagnostics.roche.com/global/en/products/tests/ventana-pd-l1-
_sp263-assay2.html
8 O’Malley DP, Yang Y, Boisot S, et al. Immunohistochemical detection of PD-L1 among diverse human neoplasms in a reference laboratory: observations based upon 62,896 cases. Mod Pathol, 2019, 32(7): 929-942. doi: 10.1038/s41379-019-0210-3
9 H i r s c h F R , M c e l h i n n y A , S t a n f o r t h D , e t a l . P D - L 1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol, 2017, 12(2): 208-222. doi: 10.1016/j.jtho.2016.11.2228
10 Tsao MS, Kerr KM, Kockx M, et al. PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol, 2018, 13(9): 1302-1311. doi: 10.1016/ j.jtho.2018.05.013
11 Yuan P, Guo CY, Li Y, et al. Consistency of PD-L1 immunohistochemical detec t ion plat for ms i n biops y sa mples w i t h adva nced lu ng adenocarcinoma: a multicenter study. Zhonghua Bing Li Xue Za Zhi,
2018, 47(11): 840-844. [袁培, 郭嫦媛, 李媛, 等. 晚期肺腺癌活检标本
PD-L1免疫组织化学多平台检测一致性研究. 中华病理学杂志, 2018,
47(11): 840-844.] doi: 10.3760/cma.j.issn.0529-5807.2018.11.005
12 Instructions for pembrolizumab injection, amended on September 29, 2019. [帕博利珠单抗注射液说明书. 修改日期2019年9月29日.]
13 Instructions for nivolumab injection, amended on March 11, 2020. [纳武利尤单抗注射液说明书. 修改日期2020年3月11日.]
14 PD-L1 inhibitor durvalumab was approved in China. Available at: https://www.astrazeneca.com.cn/zh/media/press-releases/2019/
_pd-l1_.html
15 Instructions for atezolizumab injection, amended on August 17, 2020. [
阿替利珠单抗注射液说明书. 修改日期2020年8月17日.]
16 Chinese Society of Clinical Oncology (CSCO). Guidelines for Diagnosis and Treatment of Primary Lung Cancer (2019 edition). People's Health Publishing House. [中国临床肿瘤学会(CSCO). 原发
性肺癌诊疗指南(2019版). 人民卫生出版社.]
17 Reck M, Rodríguez-Abreu D, Robinson AG, et al. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol, 2019, 37(7): 537-546. doi: 10.1200/JCO.18.00149
18 Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med, 2016, 375(19): 1823-1833. doi: 10.1056/NEJMoa1606774
19 Lopes G, Wu YL, Kudaba I, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as f i rst-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS)≥1%: open-label, phase 3 KEYNOTE-042 study. J Clin Oncol, 2018, 36(18 suppl): LBA4. doi: 10.1200/JCO.2018.36.18_suppl.LBA4
20 NCCN Clinical Practice Guidelines for non-small cell lung cancer (version 3.2020). Available at: https://www.nccn.org/
21 Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet, 2019, 393(10183): 1819-1830. doi: 10.1016/S0140-6736(18)32409-7
22 Harrington KJ, Ferris RL, Blumenschein G Jr, et al. Nivolumab versus standard, single-agent therapy of investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality- of-life results f rom a randomised, phase 3 trial. Lancet Oncol, 2017, 18(8): 1104-1115. doi: 10.1016/ S1470-2045(17)30421-7
23 Heymann JJ, Bulman WA, Swinarski D, et al. PD‐L1 expression in non‐small cell lung carcinoma: comparison among cytology, small biopsy, and surgical resection specimens. Cancer Cytopathol, 2017, 125(12): 896-907. doi: 10.1002/cncy.21937
24 Skov BG, Skov T. Paired comparison of PD-L1 expression on cytologic and histologic specimens from malignancies in the lung assessed with PD-L1 IHC 28-8pharm Dx and PD-L1 IHC 22C3pharm Dx. Appl Immunohistochem Mol Morphol, 2017, 25(7): 453-459. doi: 10.1097/ PAI.0000000000000540
25 Lozano MD, Abengozar‐Muela M, Echeveste JI, et al. Programmed death-ligand 1 expression on direct Pap‐stained cytology smears from non-small cell lung cancer: Comparison with cell blocks and surgical resection specimens. Cancer Cytopathol, 2019, 127(7): 470-480. doi: 10.1002/cncy.22155
26 Kuempers C, van der Linde LIS, Reischl M, et al. Comparison of PD-L1 expression between paired cytologic and histologic specimens from
non-small cell lung cancer patients. Virchows Arch, 2020, 476(2): 261-271. doi: 10.1007/s00428-019-02632-7
27 C a p i z z i E , R i c c i C , G i u n c h i F, e t a l . Va l i d a t i o n o f t h e immunohistochemical expression of programmed death ligand 1 (PD-L1) on cytological smears in advanced non small cell lung cancer. Lung Cancer, 2018, 126: 9-14. doi: 10.1016/j.lungcan.2018.10.017
28 Li Y, Chen J. Current challenges with PD-L1 testing for immunotherapy
biomarkers in non-small cell lung cancer. Zhonghua Bing Li Xue Za Zhi, 2019, 48(8): 585-589. [李媛, 陈杰. PD-L1检测在非小细胞肺癌
免疫治疗标志物筛选中面临的挑战. 中华病理学杂志, 2019, 48(8):
585-589.] doi: 10.3760/cma.j.issn.0529?5807.2019.08.001
29 Midha A, Sharpe A, Scott M, et al. PD-L1 expression in advanced NSCLC: Primary lesions versus metastatic sites and impact of sample age. J Clin Oncol, 2016, 34(15 suppl): 3025. doi: 10.1200/JCO.2016.34
.15_suppl.3025
30 Tsao M S , K e r r K M , Dac i c S , e t a l . I A S L C A t l a s of PD - L 1 Immunohistochemistry testing in lung cancer. 1st ed. Aurora: International Association for the Study of Lung Cancer, 2017.
31 Hewitt SM, Robinowitz M, Bogen SA, et al. Quality assurance for design control and implementation of immunohistochemistry assays: Approved guideline. 2nd ed. Wayne: Clinical and Laboratory Standards Institute, 2011. 75-76.
32 Guo XJ, Cao H, Zhou JY, et al. Progress on the Study of PD-L1 Detection Methods in Non-small Cell Lung Cancer. Zhongguo Fei Ai
Za Zhi, 2019, 22(1): 46-50. [郭雪晶, 曹赫, 周建娅, 等. PD-L1检测方
法在非小细胞肺癌的研究进展. 中国肺癌杂志, 2019, 22(1): 46-50.]
doi: 10.3779/j.issn.1009-3419.2019.01.08
33 Lin DM. Current Status of PD-L1 Testing in Non-small cell lung cancer in China. Zhonghua Bing Li Xue Za Zhi, 2017, 46(10): 665-668. [林冬梅. 中国非小细胞肺癌PD-L1检测现状. 中华病理学杂志, 2017, 46(10): 665-668.] doi: 10.3760/cma.j.issn.0529-5807.2017.10.001
34 Jiang LL, Li Y, Ying JM. Detection of PD-L1 Expression in Non-Small
Cell Lung Cancer: Current Status. Zhonghua Bing Li Xue Za Zhi, 2018, 47(11): 887-890. [蒋莉莉, 李媛, 应建明. 非小细胞肺癌PD-L1表
达检测及应用现状. 中华病理学杂志, 2018, 47(11): 887-890.] doi:
10.3760/cma.j.issn.0529-5807.2018.11.021
35 Elfving H, Mattsson JSM, Lindskog C, et al. Programmed cell death ligand 1 immunohistochemistry: a concordance study between surgical specimen, biopsy, and tissue microarray. Clin Lung Cancer, 2019, 20(4): 258-262. doi: 10.1016/j.cllc.2019.02.012
36 Sakata KK, Midthun DE, Mullon JJ, et al. Comparison of programmed death ligand-1 immunohistochemical staining between endobronchial ultrasound transbronchial needle aspiration and resected lung cancer specimens. Chest, 2018, 154(4): 827-837. doi: 10.1016/ j.chest.2018.07.017
37 Kitazono S, Fujiwara Y, Tsuta K, et al. Reliability of small biopsy samples compared with resected specimens for the determination of programmed death-ligand 1 expression in non-small-cell lung cancer. Clin Lung Cancer, 2015, 16(5): 385 -390. doi: 10.1016/
j.cllc.2015.03.008
38 Ilie M, Long-Mira E, Bence C, et al. Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti- PD-L1 therapeutic strategies. Ann Oncol, 2016, 27(1): 147-153. doi: 10.1093/annonc/mdv489
39 Miao Q , Lin G, Xu HP, et al. PD-L1 (SP142) Expression in Resected Specimens and Paired Tissue Microarrays Removed during Surgery for
Non-Small Cell Lung Cancer. Zhong Liu Yu Fang Yu Zhi Liao, 2019, 32(9): 823-830. [苗茜, 林根, 徐海鹏, 等. 程序性细胞死亡配体1在非小细胞肺癌手术切除标本及配对组织芯片中的表达分析. 肿瘤预防与治疗, 2019, 32(9): 823-830.] doi: 10.3969/j.issn.1674-0904.2019.
09.011
40 Li C, Huang C, Mok TS, et al. Comparison of 22C3 PD-L1 expression between surgically resected specimens and paired tissue microarrays in non-small cell lung cancer. J Thorac Oncol, 2017, 12(10): 1536-1543. doi: 10.1016/j.jtho.2017.07.015
41 Munar i E , Zamboni G, Marconi M, e t al . PD- L1 ex pression heterogeneity in non-small cell lung cancer: evaluation of small biopsies reliability. Oncotarget, 2017, 8(52): 90123-90131. doi: 10.18632/ oncotarget.21485
42 Mu na r i E , Za mbon i G, Lu na rd i G, e t a l . PD - L1 ex pression heterogeneity in non-small cell lung cancer: defining criteria for harmonization between biopsy specimens and whole sections. J Thorac Oncol, 2018, 13(8): 1113-1120. doi: 10.1016/j.jtho.2018.04.017
43 Saito Y, Horiuchi S, Morooka H, et al. Inter-tumor heterogeneity of PD-L1 expression in non-small cell lung cancer. J Thorac Dis, 2019, 11(12): 4982-4991. doi: 10.21037/jtd.2019.12.24
44 Luo L, Luo X, Chen W, et al. Consistency analysis of programmed death-ligand 1 expression between primary and metastatic non-small cell lung cancer: a retrospective study. J Cancer, 2020, 11(4): 974-982. doi: 10.7150/jca.34793
45 Munari E, Zamboni G, Lunardi G, et al. PD-L1 expression comparison between primar y and relapsed non- small cell lung carcinoma using whole sections and clone SP263. Oncotarget, 2018, 9(54): 30465-30471. doi: 10.18632/oncotarget.25770
46 Ta kamor i S , Toyokawa G, Okamoto I , e t al . Discrepanc y i n programmed cell death-ligand 1 between primary and metastatic non- small cell lung cancer. Anticancer Res, 2017, 37(8): 4223-4228. doi: 10.21873/anticanres.11813
47 Kim S, Koh J, Kwon D, et al. Comparative analysis of PD-L1 expression between primary and metastatic pulmonary adenocarcinomas. Eur J Cancer, 2017, 75: 141-149. doi: 10.1016/j.ejca.2017.01.004
48 Gatalica Z, Senarathne J, Vranic S. PD-L1 expression patterns in the metastatic tumors to the lung: A comparative study with the primary non-small cell lung cancer. Ann Oncol, 2017, 28(suppl_2): ii52-ii55. doi: 10.1093/annonc/mdx094
49 Senarathne W, Gates P, Vranic S, et al. Laboratory investigation. New York: Nature Publishing Group, 2017, 97: 494A-494A.
50 Kim HR, Cha YJ, Hong MH, et al. Concordance of programmed death-ligand 1 expression between primary and metastatic non- small cell lung cancer by immunohistochemistry and RNA in situ hybridization. Oncotarget, 2017, 8(50): 87234-87243. doi: 10.18632/ oncotarget.20254
51 Hong L, Negrao MV, Dibaj SS, et al. Programmed death ligand 1 heterogeneity and its Impact on benefit from immune checkpoint inhibitors in non-small-cell lung cancer. J Thorac Oncol, 2020, 15(9): 1449-1459. doi: 10.1016/j.jtho.2020.04.026
52 Takahashi T, Tateishi A, Bychkov A, et al. Remarkable alteration of PD-L1 expression after immune checkpoint therapy in patients with non-small-cell lung cancer: Two autopsy case reports. Int J Mol Sci, 2019, 20(10): 2578. doi: 10.3390/ijms20102578
53 Haratake N, Toyokawa G, Tagawa T, et al . Positive conversion of PD-L1 expression after treatments with chemotherapy and nivolumab. Anticancer Res, 2017, 37(10): 5713-5717. doi: 10.21873/ anticanres.12009
54 Shin J , Chung J H, K im SH, e t al . Ef fect of platinum- based chemotherapy on PD-L1 expression on tumor cells in non-small cell lung cancer. Cancer Res Treat, 2019, 51(3): 1086-1097. doi: 10.4143/ crt.2018.537
55 Rojkó L, Reiniger L, Téglási V, et al. Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients. J Cancer Res Clin Oncol, 2018, 144(7): 1219-1226. doi: 10.1007/ s00432-018-2642-4
56 Sheng J, Fang W, Yu J, et al. Expression of programmed death ligand-1 on tumor cells varies pre and post chemotherapy in non-small cell lung cancer. Sci Rep, 2016, 6: 20090. doi: 10.1038/srep20090
57 Sakai H, Takeda M, Sakai K, et al. Impact of cytotoxic chemotherapy on PD-L1 expression in patients with non-small cell lung cancer negative for EGFR mutation and ALK fusion. Lung Cancer, 2019, 127: 59-65. doi: 10.1016/j.lungcan.2018.11.025
58 Choe EA, Cha Y J, K im JH, et al . Dynamic changes in PD-L1 expression and CD8+ T cell infiltration in non-small cell lung cancer following chemoradiation therapy. Lung Cancer, 2019, 136: 30-36. doi: 10.1016/j.lungcan.2019.07.027
59 Fujimoto D, Uehara K, Sato Y, et al. Alteration of PD-L1 expression and its prognostic impact after concurrent chemoradiation therapy in
non-small cell lung cancer patients. Sci Rep, 2017, 7(1): 11373. doi: 10.1038/s41598-017-11949-9
60 Omori S, Kenmotsu H, Abe M, et al. Changes in programmed death ligand 1 expression in non-small cell lung cancer patients who received anticancer treatments. Int J Clin Oncol, 2018, 23(6): 1052-1059. doi: 10.1007/s10147-018-1305-4
61 Han JJ, Kim DW, Koh J, et al. Change in PD-L1 expression after acquiring resistance to gefitinib in EGFR-mutant non-small-cell lung cancer. Clin Lung Cancer, 2016, 17(4): 263-270. doi: 10.1016/
j.cllc.2015.11.006
非小细胞肺癌PD-L1免疫组织化学检测规范中国专家共识专家组成员
(按姓氏汉语拼音排名)
|
医院 |
姓名 |
参与专家 |
南京大学医学院附属鼓楼医院 |
樊祥山 |
参与专家 |
复旦大学附属中山医院 |
侯英勇 |
参与专家 |
四川大学华西医院 |
蒋莉莉 |
参与专家 |
复旦大学附属肿瘤医院 |
李媛 |
参与专家 |
北京大学肿瘤医院 |
林冬梅 |
参与专家 |
中山大学附属肿瘤医院 |
林素暇 |
参与专家 |
上海交通大学附属胸科医院上海市肺部肿瘤临床医学中心 |
陆舜 |
参与专家 |
中国科学院大学附属肿瘤医院 |
孙文勇 |
参与专家 |
华中科技大学同济医学院附属同济医院 |
王国平 |
参与专家 |
吉林大学第一医院 |
王银萍 |
参与专家 |
北京医院 |
王征 |
参与专家 |
同济大学附属上海市肺科医院 |
武春燕 |
参与专家 |
山西省肿瘤医院 |
郗彦凤 |
参与专家 |
广东省人民医院广东省医学科学院 |
颜黎栩 |
参与专家 |
中国医科大学附属盛京医院 |
杨向红 |
参与专家 |
湖北省肿瘤医院 |
岳君秋 |
参与专家 |
广东省人民医院广东省肺癌研究所 |
张绪超 |
参与专家 |
天津医科大学附属肿瘤医院 |
赵纲 |
Cite this article as: Chinese Anti-Cancer Association, Lung Cancer Study Group of Committee of Oncopathology, Chinese Society of Lung Cancer, Expert Group on PD-L1 Testing Consensus. Chinese Expert Consensus on Standards of PD-L1 Immunohistochemistry Testing for Non-small Cell Lung Cancer. Zhongguo Fei Ai Za Zhi, 2020, 23(9): 733-740. [中国抗癌协会肿瘤病理专业委员会肺癌学组, 中国抗癌协会肺癌专业委员会, PD-L1检测共识专家组. 非小细胞肺癌PD-L1免疫组织化学检测规范中国专家共识. 中国肺癌杂志, 2020, 23(9):733-740.] doi: 10.3779/j.issn.1009-3419.2020.101.43