Multicentre study on the consistency of PD-L1 immunohistochemistry as predictive test for immunotherapy in non-small cell lung cancer

Rogier Butter*, Nils A 't Hart, Gerrit K J Hooijer, Kim Monkhorst, Ernst-Jan Speel, Paul Theunissen, Erik Thunnissen, Jan H Von der Thüsen, Wim Timens, Marc J van de Vijver

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

AIMS: Investigate the impact of interlaboratory- and interobserver variability of immunohistochemistry on the assessment of programmed death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC).

METHODS: Two tissue microarrays (TMAs) were constructed from 50 (TMA-A) and 51 (TMA-B) resected NSCLC cases, and distributed among eight centres. Immunostaining for PD-L1 was performed using Agilent's 22C3 pharmDx Assay (pharmDx) and/or a 22C3 laboratory developed test (LDT). The interlaboratory variability of staining- and interobserver variability of scoring for PD-L1 were assessed in selected critical samples (samples at the cut-off of positivity) and non-critical samples. Also, PD-L1 epitope deterioration in time in stored unstained slides was analysed. Krippendorff's alpha values (0=maximal, 1=no variability) were calculated as measure for variability.

RESULTS: For interlaboratory variability of immunostaining, the percentage of PD-L1 positive cases among centres ranged 40%-51% (1% cut-off) and 23%-30% (50% cut-off). Alpha values at 1% cut-off were 0.88 (pharmDx) and 0.87 (LDT) and at 50% cut-off 0.82 (pharmDx) and 0.95 (LDT). Interobserver variability of scoring resulted in PD-L1 positive cases ranging 29%-55% (1% cut-off) and 14%-30% (50% cut-off) among pathologists. Alpha values were at 1% cut-off 0.83 (TMA-A) and 0.66 (TMA-B), and at 50% cut-off 0.77 (TMA-A) and 0.78 (TMA-B). Interlaboratory variability of staining was higher (p<0.001) in critical samples than in non-critical samples at 50% cut-off. Furthermore, PD-L1 epitope deterioration in unstained slides was observed after 12 weeks.

CONCLUSIONS: The results provide insight in factors contributing to variability of immunohistochemical assessment of PD-L1, and contribute to more reliable predictive testing for PD-L1.

Original languageEnglish
Pages (from-to)423-430
Number of pages8
JournalJournal of Clinical Pathology
Volume73
Issue number7
Early online date10 Dec 2019
DOIs
Publication statusPublished - Jul 2020

Keywords

  • lung cancer
  • immunohistochemistry
  • oncology
  • pulmonary pathology
  • histopathology
  • SQUAMOUS-CELL
  • OPEN-LABEL
  • EXPRESSION
  • DOCETAXEL
  • PEMBROLIZUMAB
  • BLOCKADE
  • ASSAY
  • HETEROGENEITY
  • ATEZOLIZUMAB
  • NIVOLUMAB

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