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dc.contributor.authorHumphries, MP
dc.contributor.authorMcQuaid, S
dc.contributor.authorCraig, SG
dc.contributor.authorBingham, V
dc.contributor.authorMaxwell, P
dc.contributor.authorMaurya, M
dc.contributor.authorMcLean, F
dc.contributor.authorSampson, J
dc.contributor.authorHiggins, P
dc.contributor.authorGreene, C
dc.contributor.authorJames, J
dc.contributor.authorSalto-Tellez, M
dc.date.accessioned2020-08-28T10:26:18Z
dc.date.issued2019-01
dc.identifier.citationJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2019, 14 (1), pp. 45 - 53
dc.identifier.issn1556-0864
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4056
dc.identifier.eissn1556-1380
dc.identifier.doi10.1016/j.jtho.2018.09.025
dc.description.abstractIntroduction Patient suitability to anti-programmed death ligand 1 (PD-L1) immune checkpoint inhibition is key to the treatment of NSCLC. We present, applied to PD-L1 testing: a comprehensive cross-validation of two immunohistochemistry (IHC) clones; our descriptive experience in diagnostic reflex testing; the concordance of IHC to in situ RNA (RNA-ISH); and application of digital pathology.Methods Eight hundred thirteen NSCLC tumor samples collected from 564 diagnostic samples were analyzed prospectively, and 249 diagnostic samples analyzed retrospectively in tissue microarray format. Validated methods for IHC and RNA-ISH were tested in tissue microarrays and full sections and the QuPath system were used for digital pathology analysis.Results Antibody concordance of clones SP263 and 22C3 validation was 97% to 98% in squamous cell carcinoma and adenocarcinomas, respectively. Clinical NSCLC cases were reported as PD-L1-negative (48%), 1% to 49% (23%), and more than 50% (29%), with differences associated to tissue-type and EGFR status. Comparison of IHC and RNA-ISH was highly concordant in both subgroups. Comparison of digital assessment versus manual assessment was highly concordant. Discrepancies were mostly around the 1% clinical threshold. Challenging IHC interpretation included 1) calculating the total tumor cell denominator and the nature of PD-L1 expressing cell aggregates in cytology samples; 2) peritumoral expression of positive immune cells; 3) calculation of positive tumor percentages around clinical thresholds; and 4) relevance of the 100 malignant cell rule.Conclusions Sample type and EGFR status dictate differences in the expected percentage of PD-L1 expression. Analysis of PD-L1 is challenging, and interpretative guidelines are discussed. PD-L1 evaluations by RNA-ISH and digital pathology appear reliable, particularly in adenocarcinomas.
dc.formatPrint-Electronic
dc.format.extent45 - 53
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectCarcinoma, Non-Small-Cell Lung
dc.subjectLung Neoplasms
dc.subjectProgrammed Cell Death 1 Receptor
dc.titleCritical Appraisal of Programmed Death Ligand 1 Reflex Diagnostic Testing: Current Standards and Future Opportunities.
dc.typeJournal Article
dcterms.dateAccepted2018-09-28
rioxxterms.versionofrecord10.1016/j.jtho.2018.09.025
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
pubs.publication-statusPublished
pubs.volume14
pubs.embargo.termsNot known
icr.researchteamIntegrated Pathologyen_US
dc.contributor.icrauthorSalto-Tellez, Manuelen


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