PD-L1 immunohistochemistry in non-small-cell lung cancer: unraveling differences in staining concordance and interpretation

Cleo Keppens; Elisabeth Mc Dequeker; Patrick Pauwels; Ales Ryska; Nils ‘t Hart; Jan H. von der Thüsen

doi:10.1007/s00428-020-02976-5

PD-L1 immunohistochemistry in non-small-cell lung cancer: unraveling differences in staining concordance and interpretation

Cleo Keppens
, Elisabeth Mc Dequeker
, Patrick Pauwels
, Ales Ryska
, Nils ‘t Hart
, Jan H. von der Thüsen^*

^*Corresponding author for this work

Pathology

KU Leuven
University of Antwerp
Antwerp University Hospital
Charles University
University Medical Centre Groningen
Isala Clinics

Research output: Contribution to journal › Article › Academic › peer-review

18 Citations (Scopus)

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Abstract

Programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) is accepted as a predictive biomarker for the selection of immune checkpoint inhibitors. We evaluated the staining quality and estimation of the tumor proportion score (TPS) in non-small-cell lung cancer during two external quality assessment (EQA) schemes by the European Society of Pathology. Participants received two tissue micro-arrays with three (2017) and four (2018) cases for PD-L1 IHC and a positive tonsil control, for staining by their routine protocol. After the participants returned stained slides to the EQA coordination center, three pathologists assessed each slide and awarded an expert staining score from 1 to 5 points based on the staining concordance. Expert scores significantly (p < 0.01) improved between EQA schemes from 3.8 (n = 67) to 4.3 (n = 74) on 5 points. Participants used 32 different protocols: the majority applied the 22C3 (56.7%) (Dako), SP263 (19.1%) (Ventana), and E1L3N (Cell Signaling) (7.1%) clones. Staining artifacts consisted mainly of very weak or weak antigen demonstration (63.0%) or excessive background staining (19.8%). Participants using CE-IVD kits reached a higher score compared with those using laboratory-developed tests (LDTs) (p < 0.05), mainly attributed to a better concordance of SP263. The TPS was under- and over-estimated in 20/423 (4.7%) and 24/423 (5.7%) cases, respectively, correlating to a lower expert score. Additional research is needed on the concordance of less common protocols, and on reasons for lower LDT concordance. Laboratories should carefully validate all test methods and regularly verify their performance. EQA participation should focus on both staining concordance and interpretation of PD-L1 IHC.

Original language	English
Pages (from-to)	827-839
Number of pages	13
Journal	Virchows Archiv
Volume	478
Issue number	5
Early online date	4 Dec 2020
DOIs	https://doi.org/10.1007/s00428-020-02976-5
Publication status	Published - May 2021

Bibliographical note

Funding Information:
The Biomedical Quality Assurance Research Unit received an unrestricted research grant from Pfizer Oncology for the coordination of the EQA scheme in 2017 and 2018. The European Society of Pathology received a grant from Bristol-Myers Squibb (BMS) for the organization of the 2017 and 2018 PD-L1 EQA schemes. Both sources of funding were awarded irrespective of the presented research; grant numbers are not applicable.

Funding Information:
This project would not have been possible without the support of the following people: The participating laboratories in the 2017-2018 EQA schemes The European Society of Pathology for the support in administration of organizing the EQA schemes Financial grants of Bristol-Myers-Squibb and AstraZeneca received by ESP to support the EQA schemes Ivonne Marondel from Pfizer Oncology for the unrestricted research grant for coordination of the schemes Colleagues of the BQA Research unit for the coordination and administrative support V?ronique Tack for conceptualization of the laboratory setting taxonomy The scheme experts, assessors and members of the steering committee Universital Hospital Antwerp for the use of the multi-head microscope Annouschka Laenen, Leuven Biostatistics and Statistical Bio-informatics Centre (L-BioStat) and the Leuven Cancer Institute for performing the statistical analyses

Publisher Copyright:
© 2020, The Author(s).

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PD-L1 immunohistochemistry in non-small-cell lung cancer, unraveling differences in staining concordance and interpretationFinal published version, 2.58 MBLicence: CC BY

Cite this

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title = "PD-L1 immunohistochemistry in non-small-cell lung cancer: unraveling differences in staining concordance and interpretation",

abstract = "Programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) is accepted as a predictive biomarker for the selection of immune checkpoint inhibitors. We evaluated the staining quality and estimation of the tumor proportion score (TPS) in non-small-cell lung cancer during two external quality assessment (EQA) schemes by the European Society of Pathology. Participants received two tissue micro-arrays with three (2017) and four (2018) cases for PD-L1 IHC and a positive tonsil control, for staining by their routine protocol. After the participants returned stained slides to the EQA coordination center, three pathologists assessed each slide and awarded an expert staining score from 1 to 5 points based on the staining concordance. Expert scores significantly (p < 0.01) improved between EQA schemes from 3.8 (n = 67) to 4.3 (n = 74) on 5 points. Participants used 32 different protocols: the majority applied the 22C3 (56.7\%) (Dako), SP263 (19.1\%) (Ventana), and E1L3N (Cell Signaling) (7.1\%) clones. Staining artifacts consisted mainly of very weak or weak antigen demonstration (63.0\%) or excessive background staining (19.8\%). Participants using CE-IVD kits reached a higher score compared with those using laboratory-developed tests (LDTs) (p < 0.05), mainly attributed to a better concordance of SP263. The TPS was under- and over-estimated in 20/423 (4.7\%) and 24/423 (5.7\%) cases, respectively, correlating to a lower expert score. Additional research is needed on the concordance of less common protocols, and on reasons for lower LDT concordance. Laboratories should carefully validate all test methods and regularly verify their performance. EQA participation should focus on both staining concordance and interpretation of PD-L1 IHC.",

author = "Cleo Keppens and Dequeker, \{Elisabeth Mc\} and Patrick Pauwels and Ales Ryska and \{{\textquoteleft}t Hart\}, Nils and \{von der Th{\"u}sen\}, \{Jan H.\}",

note = "Funding Information: The Biomedical Quality Assurance Research Unit received an unrestricted research grant from Pfizer Oncology for the coordination of the EQA scheme in 2017 and 2018. The European Society of Pathology received a grant from Bristol-Myers Squibb (BMS) for the organization of the 2017 and 2018 PD-L1 EQA schemes. Both sources of funding were awarded irrespective of the presented research; grant numbers are not applicable. Funding Information: This project would not have been possible without the support of the following people: The participating laboratories in the 2017-2018 EQA schemes The European Society of Pathology for the support in administration of organizing the EQA schemes Financial grants of Bristol-Myers-Squibb and AstraZeneca received by ESP to support the EQA schemes Ivonne Marondel from Pfizer Oncology for the unrestricted research grant for coordination of the schemes Colleagues of the BQA Research unit for the coordination and administrative support V?ronique Tack for conceptualization of the laboratory setting taxonomy The scheme experts, assessors and members of the steering committee Universital Hospital Antwerp for the use of the multi-head microscope Annouschka Laenen, Leuven Biostatistics and Statistical Bio-informatics Centre (L-BioStat) and the Leuven Cancer Institute for performing the statistical analyses Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2021",

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doi = "10.1007/s00428-020-02976-5",

language = "English",

volume = "478",

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T2 - unraveling differences in staining concordance and interpretation

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AU - Ryska, Ales

AU - ‘t Hart, Nils

AU - von der Thüsen, Jan H.

N1 - Funding Information: The Biomedical Quality Assurance Research Unit received an unrestricted research grant from Pfizer Oncology for the coordination of the EQA scheme in 2017 and 2018. The European Society of Pathology received a grant from Bristol-Myers Squibb (BMS) for the organization of the 2017 and 2018 PD-L1 EQA schemes. Both sources of funding were awarded irrespective of the presented research; grant numbers are not applicable. Funding Information: This project would not have been possible without the support of the following people: The participating laboratories in the 2017-2018 EQA schemes The European Society of Pathology for the support in administration of organizing the EQA schemes Financial grants of Bristol-Myers-Squibb and AstraZeneca received by ESP to support the EQA schemes Ivonne Marondel from Pfizer Oncology for the unrestricted research grant for coordination of the schemes Colleagues of the BQA Research unit for the coordination and administrative support V?ronique Tack for conceptualization of the laboratory setting taxonomy The scheme experts, assessors and members of the steering committee Universital Hospital Antwerp for the use of the multi-head microscope Annouschka Laenen, Leuven Biostatistics and Statistical Bio-informatics Centre (L-BioStat) and the Leuven Cancer Institute for performing the statistical analyses Publisher Copyright: © 2020, The Author(s).

PY - 2021/5

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N2 - Programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) is accepted as a predictive biomarker for the selection of immune checkpoint inhibitors. We evaluated the staining quality and estimation of the tumor proportion score (TPS) in non-small-cell lung cancer during two external quality assessment (EQA) schemes by the European Society of Pathology. Participants received two tissue micro-arrays with three (2017) and four (2018) cases for PD-L1 IHC and a positive tonsil control, for staining by their routine protocol. After the participants returned stained slides to the EQA coordination center, three pathologists assessed each slide and awarded an expert staining score from 1 to 5 points based on the staining concordance. Expert scores significantly (p < 0.01) improved between EQA schemes from 3.8 (n = 67) to 4.3 (n = 74) on 5 points. Participants used 32 different protocols: the majority applied the 22C3 (56.7%) (Dako), SP263 (19.1%) (Ventana), and E1L3N (Cell Signaling) (7.1%) clones. Staining artifacts consisted mainly of very weak or weak antigen demonstration (63.0%) or excessive background staining (19.8%). Participants using CE-IVD kits reached a higher score compared with those using laboratory-developed tests (LDTs) (p < 0.05), mainly attributed to a better concordance of SP263. The TPS was under- and over-estimated in 20/423 (4.7%) and 24/423 (5.7%) cases, respectively, correlating to a lower expert score. Additional research is needed on the concordance of less common protocols, and on reasons for lower LDT concordance. Laboratories should carefully validate all test methods and regularly verify their performance. EQA participation should focus on both staining concordance and interpretation of PD-L1 IHC.

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PD-L1 immunohistochemistry in non-small-cell lung cancer: unraveling differences in staining concordance and interpretation

Abstract

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