Critical Appraisal of Programmed Death Ligand 1 Reflex Diagnostic Testing: Current Standards and Future Opportunities.
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ICR Authors
Authors
Humphries, MP
McQuaid, S
Craig, SG
Bingham, V
Maxwell, P
Maurya, M
McLean, F
Sampson, J
Higgins, P
Greene, C
James, J
Salto-Tellez, M
McQuaid, S
Craig, SG
Bingham, V
Maxwell, P
Maurya, M
McLean, F
Sampson, J
Higgins, P
Greene, C
James, J
Salto-Tellez, M
Document Type
Journal Article
Date
2019-01-01
Date Accepted
2018-09-28
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.
Citation
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2019, 14 (1), pp. 45 - 53
Source Title
Publisher
ELSEVIER SCIENCE INC
ISSN
1556-0864
eISSN
1556-1380
Collections
Research Team
Integrated Pathology