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

Brunnström, Hans (author)
Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,Regional Laboratories Region Skåne
Johansson, Anna (author)
Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups
Westbom-Fremer, Sofia (author)
Reg Labs Reg Skane, Dept Pathol, SE-22185 Lund, Sweden.,Regional Laboratories Region Skåne
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Backman, Max (author)
Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
Djureinovic, Dijana (author)
Uppsala University,Uppsala universitet,Klinisk och experimentell patologi
Patthey, Annika (author)
Umea Univ Hosp, Dept Pathol, Umea, Sweden.,Norrland University Hospital
Isaksson-Mettvainio, Martin (author)
Umea Univ Hosp, Dept Pathol, Umea, Sweden.,Norrland University Hospital
Gulyas, Miklos (author)
Uppsala University,Uppsala universitet,Klinisk och experimentell patologi
Micke, Patrick (author)
Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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 (creator_code:org_t)
NATURE PUBLISHING GROUP, 2017
2017
English.
In: Modern Pathology. - : NATURE PUBLISHING GROUP. - 0893-3952 .- 1530-0285. ; 30:10, s. 1411-1421
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)

Keyword

Patologi
Pathology

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