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J Thorac Oncol. 2018 Oct 5. pii: S1556-0864(18)33177-0. doi: 10.1016/j.jtho.2018.09.025. [Epub ahead of print]

Critical appraisal of PD-L1 reflex diagnostic testing: current standards and future opportunities.

Author information

1
Molecular Pathology Programme, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
2
Molecular Pathology Programme, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK,; Cellular Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road; Northern Ireland Biobank, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
3
Molecular Pathology Programme, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK,; Cellular Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road.
4
Molecular Pathology Programme, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK,; Cellular Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road. Electronic address: m.salto-tellez@qub.ac.uk.

Abstract

INTRODUCTION:

Patient suitability to anti-PD-L1 immune checkpoint inhibition is key to the treatment of non-small cell lung cancer (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:

813 NSCLC tumour samples collected from 564 diagnostic samples were analysed prospectively and 249 diagnostic samples analysed retrospectively in TMA format. Validated methods for IHC and RNA-ISH were tested in TMAs and full sections and the QuPath system used for digital pathology analysis.

RESULTS:

Antibody concordance of clones SP263 and 22C3 validation was 97-98% in squamous cell carcinoma and adenocarcinomas, respectively. Clinical NSCLC cases were reported as PD-L1 negative (48%), 1-49% (23%) and >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 a) calculating the total tumour cell denominator and the nature of PD-L1 expressing cell aggregates in cytology samples; b) peritumoral expression of positive immune cells; c) calculation of positive tumour percentages around clinical thresholds; d) 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 evaluation by RNA-ISH and digital pathology appear reliable, particularly in adenocarcinomas.

KEYWORDS:

Clinical Workflow; Image Analysis; PD-L1; RNAscope; Validation

PMID:
30296485
DOI:
10.1016/j.jtho.2018.09.025

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