Inter- and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma Journal Article


Authors: Downes, M. R.; Slodkowska, E.; Katabi, N.; Jungbluth, A. A.; Xu, B.
Article Title: Inter- and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma
Abstract: Aims: Programmed death-ligand 1 (PD-L1) expression by tumour cells (TC) is a mechanism for tumour immune escape through down-regulation of antitumour T cell responses and is a target for immunotherapy. PD-L1 status as a predictor of treatment response has led to the development of multiple biomarkers with different reference cut-offs. We assessed pathologist consistency in evaluating PD-L1 immunopositivity by examining the inter- and intraobserver agreement using various antibody clones and different cancer types. Methods and results: PD-L1 expression in TC and immune cells (IC) was manually scored in 27 head and neck squamous cell carcinoma (HSCC), 30 urothelial carcinoma (UC) and breast carcinoma (BC) using three commercial clones (SP263, SP142, 22C3) and one platform-independent test (E1L3N). For interobserver agreement, PD-L1 status was evaluated blindly by three pathologists. For intraobserver agreement, PD-L1 expression was re-evaluated following a wash-out period. Intraclass correlation coefficient (ICC), overall percentage agreement (OPA) and κ-values were calculated. Using clinical algorithms, the percentage of PD-L1-positive cases in HSCC, BC and UC were 15–81%, 47–67% and 7–43%, respectively. The percentage of PD-L1 positive cases relied heavily on the algorithm/cut-off values used. Almost perfect interobserver agreement was achieved using SP263 and E1L3N in HSCC, 22C3, SP142 and E1L3N in BC and 22C3 in UC. The SP142 clone in UC and HSCC showed moderate agreement and was associated with lower ICC and decreased intraobserver concordance. Conclusions: Excellent inter- and intraobserver agreement can be achieved using SP263, 22C3 and E1L3N, whereas PD-L1 scoring using SP142 clone is associated with a higher level of subjectivity. © 2019 John Wiley & Sons Ltd
Keywords: controlled study; human tissue; protein expression; major clinical study; retrospective study; correlation coefficient; algorithm; breast carcinoma; urothelial carcinoma; scoring system; cell clone; transitional cell carcinoma; pathologist; immunocompetent cell; carcinoma cell; head and neck carcinoma; programmed death 1 ligand 1; head and neck squamous cell carcinoma; interrater reliability; intrarater reliability; human; priority journal; article; assay comparison; pd-l1 immunohistochemistry assay
Journal Title: Histopathology
Volume: 76
Issue: 2
ISSN: 0309-0167
Publisher: Wiley Blackwell  
Date Published: 2020-01-01
Start Page: 191
End Page: 200
Language: English
DOI: 10.1111/his.13946
PUBMED: 31243779
PROVIDER: scopus
PMCID: PMC6917963
DOI/URL:
Notes: Article -- Export Date: 3 February 2020 -- Source: Scopus
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  1. Nora Katabi
    303 Katabi
  2. Achim Jungbluth
    454 Jungbluth
  3. Bin   Xu
    227 Xu