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PD-L1 immunohistochemistry in clinical diagnostics of lung cancer : inter-pathologist variability is higher than assay variability

Brunnström, Hans LU ; Johansson, Anna LU ; Westbom-Fremer, Sofia; Backman, Max; Djureinovic, Dijana; Patthey, Annika; Isaksson-Mettävainio, Martin; Gulyas, Miklos and Micke, Patrick (2017) In Modern Pathology 30(10). p.1411-1421
Abstract

Assessment of programmed cell death ligand 1 (PD-L1) immunohistochemical staining is used for decision on treatment with programmed cell death 1 and PD-L1 checkpoint inhibitors in lung adenocarcinomas and squamous cell carcinomas. This study aimed to compare the staining properties of tumor cells between the antibody clones 28-8, 22C3, SP142, and SP263 and investigate interrater variation between pathologists to see if these stainings can be safely evaluated in the clinical setting. Using consecutive sections from a tissue microarray with tumor tissue from 55 resected lung cancer cases, staining with five PD-L1 assays (28-8 from two different vendors, 22C3, SP142, and SP263) was performed. Seven pathologists individually evaluated the... (More)

Assessment of programmed cell death ligand 1 (PD-L1) immunohistochemical staining is used for decision on treatment with programmed cell death 1 and PD-L1 checkpoint inhibitors in lung adenocarcinomas and squamous cell carcinomas. This study aimed to compare the staining properties of tumor cells between the antibody clones 28-8, 22C3, SP142, and SP263 and investigate interrater variation between pathologists to see if these stainings can be safely evaluated in the clinical setting. Using consecutive sections from a tissue microarray with tumor tissue from 55 resected lung cancer cases, staining with five PD-L1 assays (28-8 from two different vendors, 22C3, SP142, and SP263) was performed. Seven pathologists individually evaluated the percentage of positive tumor cells, scoring each sample applying cutoff levels used in clinical studies: <1% positive tumor cells (score 0), 1-4% (score 1), 5-9% (score 2), 10-24% (score 3), 25-49% (score 4), and >50% positive tumor cells (score 5). Pairwise analysis of antibody clones showed weighted kappa values in the range of 0.45-0.91 with the highest values for comparisons with 22C3 and 28-8 and the lowest involving SP142. Excluding SP142 resulted in kappa 0.75-0.91. Weighted kappa for interobserver variation between pathologists was 0.71-0.96. Up to 20% of the cases were differently classified as positive or negative by any pathologist compared with consensus score using ≥1% positive tumor cells as cutoff. A significantly better agreement between pathologists was seen using ≥50% as cutoff (0-5% of cases). In conclusion, the concordance between the PD-L1 antibodies 22C3, 28-8 and SP263 is relatively good when evaluating lung cancers and suggests that any one of these assays may be sufficient as basis for decision on treatment with nivolumab, pembrolizumab, and durvalumab. The scoring of the pathologist presents an intrinsic source of error that should be considered especially at low PD-L1 scores.Modern Pathology advance online publication, 30 June 2017; doi:10.1038/modpathol.2017.59.

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published
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in
Modern Pathology
volume
30
issue
10
pages
1411 - 1421
publisher
Nature Publishing Group
external identifiers
  • scopus:85030643064
  • wos:000412100400007
ISSN
1530-0285
DOI
10.1038/modpathol.2017.59
language
English
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yes
id
834152c5-c7f9-4e8d-a9c6-077ddd5df26d
date added to LUP
2017-07-13 09:07:11
date last changed
2018-04-22 04:30:34
@article{834152c5-c7f9-4e8d-a9c6-077ddd5df26d,
  abstract     = {<p>Assessment of programmed cell death ligand 1 (PD-L1) immunohistochemical staining is used for decision on treatment with programmed cell death 1 and PD-L1 checkpoint inhibitors in lung adenocarcinomas and squamous cell carcinomas. This study aimed to compare the staining properties of tumor cells between the antibody clones 28-8, 22C3, SP142, and SP263 and investigate interrater variation between pathologists to see if these stainings can be safely evaluated in the clinical setting. Using consecutive sections from a tissue microarray with tumor tissue from 55 resected lung cancer cases, staining with five PD-L1 assays (28-8 from two different vendors, 22C3, SP142, and SP263) was performed. Seven pathologists individually evaluated the percentage of positive tumor cells, scoring each sample applying cutoff levels used in clinical studies: &lt;1% positive tumor cells (score 0), 1-4% (score 1), 5-9% (score 2), 10-24% (score 3), 25-49% (score 4), and &gt;50% positive tumor cells (score 5). Pairwise analysis of antibody clones showed weighted kappa values in the range of 0.45-0.91 with the highest values for comparisons with 22C3 and 28-8 and the lowest involving SP142. Excluding SP142 resulted in kappa 0.75-0.91. Weighted kappa for interobserver variation between pathologists was 0.71-0.96. Up to 20% of the cases were differently classified as positive or negative by any pathologist compared with consensus score using ≥1% positive tumor cells as cutoff. A significantly better agreement between pathologists was seen using ≥50% as cutoff (0-5% of cases). In conclusion, the concordance between the PD-L1 antibodies 22C3, 28-8 and SP263 is relatively good when evaluating lung cancers and suggests that any one of these assays may be sufficient as basis for decision on treatment with nivolumab, pembrolizumab, and durvalumab. The scoring of the pathologist presents an intrinsic source of error that should be considered especially at low PD-L1 scores.Modern Pathology advance online publication, 30 June 2017; doi:10.1038/modpathol.2017.59.</p>},
  author       = {Brunnström, Hans and Johansson, Anna and Westbom-Fremer, Sofia and Backman, Max and Djureinovic, Dijana and Patthey, Annika and Isaksson-Mettävainio, Martin and Gulyas, Miklos and Micke, Patrick},
  issn         = {1530-0285},
  language     = {eng},
  number       = {10},
  pages        = {1411--1421},
  publisher    = {Nature Publishing Group},
  series       = {Modern Pathology},
  title        = {PD-L1 immunohistochemistry in clinical diagnostics of lung cancer : inter-pathologist variability is higher than assay variability},
  url          = {http://dx.doi.org/10.1038/modpathol.2017.59},
  volume       = {30},
  year         = {2017},
}