dc.contributor.author | Humphries, MP | |
dc.contributor.author | McQuaid, S | |
dc.contributor.author | Craig, SG | |
dc.contributor.author | Bingham, V | |
dc.contributor.author | Maxwell, P | |
dc.contributor.author | Maurya, M | |
dc.contributor.author | McLean, F | |
dc.contributor.author | Sampson, J | |
dc.contributor.author | Higgins, P | |
dc.contributor.author | Greene, C | |
dc.contributor.author | James, J | |
dc.contributor.author | Salto-Tellez, M | |
dc.date.accessioned | 2020-08-28T10:26:18Z | |
dc.date.issued | 2019-01-01 | |
dc.identifier.citation | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2019, 14 (1), pp. 45 - 53 | |
dc.identifier.issn | 1556-0864 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4056 | |
dc.identifier.eissn | 1556-1380 | |
dc.identifier.doi | 10.1016/j.jtho.2018.09.025 | |
dc.description.abstract | INTRODUCTION: 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.format | Print-Electronic | |
dc.format.extent | 45 - 53 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCIENCE INC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Carcinoma, Non-Small-Cell Lung | |
dc.subject | Lung Neoplasms | |
dc.subject | Programmed Cell Death 1 Receptor | |
dc.title | Critical Appraisal of Programmed Death Ligand 1 Reflex Diagnostic Testing: Current Standards and Future Opportunities. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-09-28 | |
rioxxterms.versionofrecord | 10.1016/j.jtho.2018.09.025 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer | |
pubs.issue | 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 14 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Integrated Pathology | |
dc.contributor.icrauthor | Salto-Tellez, Manuel | |