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. 2020 Jan;76(2):191-200.
doi: 10.1111/his.13946. Epub 2019 Sep 9.

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

Michelle R Downes  1   2 , Elzbieta Slodkowska  1   2 , Nora Katabi  3 , Achim A Jungbluth  3 , Bin Xu  3
Affiliations

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

Michelle R Downes et al. Histopathology. 2020 Jan.

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.

Keywords: PD-L1 immunohistochemistry assay; assay comparison; breast carcinoma; head and neck carcinoma; urothelial carcinoma.

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Figures

Figure 1
Figure 1
(A) A representative example of PD-L1 scoring. TC: tumour cells; IC: immune cells, HSCC: head and neck squamous cell carcinoma. (B) Interobserver agreement of PD-L1 evaluation using various antibody clones in HSCC, breast carcinoma (BC), and urothelial carcinoma (UC). As the cut-off value of E1L3N clone was not established, the threshold for 22C3, SP263, and SP142 antibody clones were applied.
Figure 2
Figure 2
Interobserver agreement and intraclass correlation coefficient (ICC) on raw positive percentage of tumor cells (TC) and immune cells (IC).
Figure 3
Figure 3
Intraobserver agreement of PD-L1 interpretation. Shaded squares represent cases that are interpreted as PD-L1 positive.
See this image and copyright information in PMC

Comment in

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