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Comparative Study
. 2018 Aug;42(8):1059-1066.
doi: 10.1097/PAS.0000000000001084.

PD-L1 Immunohistochemistry Assay Concordance in Urothelial Carcinoma of the Bladder and Hypopharyngeal Squamous Cell Carcinoma

Anjelica Hodgson  1   2 , Elzbieta Slodkowska  1   2 , Achim Jungbluth  3 , Stanley K Liu  4 , Danny Vesprini  5 , Danny Enepekides  5 , Kevin Higgins  5 , Nora Katabi  3 , Bin Xu  1   2 , Michelle R Downes  1   2
Affiliations
Comparative Study

PD-L1 Immunohistochemistry Assay Concordance in Urothelial Carcinoma of the Bladder and Hypopharyngeal Squamous Cell Carcinoma

Anjelica Hodgson et al. Am J Surg Pathol. 2018 Aug.

Abstract

Programmed death ligand-1 (PD-L1) immunohistochemistry is used to guide treatment decisions regarding the use of checkpoint immunotherapy in the management of urothelial carcinoma of the bladder and hypopharyngeal (HP) squamous cell carcinoma. With increasing PD-L1 testing options, a need has arisen to assess the analytical comparability of diagnostic assays in order to develop a more sustainable testing strategy. Using tissue microarrays, PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was manually scored in 197 cases and 27 cases of bladder and HP cancer, respectively. Three commercial kits (Ventana SP263, Ventana SP142, Dako 22C3) and 1 platform-independent test (Cell Signalling Technologies E1L3N) were utilized. Across the 3 commercially available clones, 14% and 74% of urothelial carcinomas were positive and negative, respectively, whereas 7% and 78% of HP carcinomas were positive and negative, respectively. Twelve percent of bladder and 15% HP cases showed discrepant PD-L1 classification results. Regardless of the scoring algorithm used, E1L3N provided comparable PD-L1 staining results. Fleiss' kappa and intraclass correlation coefficient (ICC) analyses demonstrated substantial agreement among all antibody clones (k=0.639 to 0.791) and excellent reliability among SP263, 22C3, and E1L3N antibodies (ICC, 0.929 to 0.949) in TC staining. Compared with the other 3 clones, SP142 TC staining was lower with only moderate correlation (ICC, 0.500 to 0.619). Generally, the reliability of immune cell staining was lower compared with TC staining (ICC, 0.519 to 0.866). Our results demonstrate good analytic comparability of all 4 antibodies. The results are encouraging and support growing optimism in the pathology and oncology communities concerning strategies in PD-L1 assay use.

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Conflict of interest statement

Conflict of interest disclosure statements:

• Dr. Downes has received compensation from Hoffman – La Roche and Astra Zeneca for participating on advisory boards and honoraria from Astra Zeneca.

• Dr. Xu has received honoraria from Merck.

Figures

Figure 1.
Figure 1.
Representative H&E of urothelial carcinoma (UC) and hypopharyngeal squamous cell carcinoma (HP-SCC) with corresponding PD-L1 staining with each antibody clone.
Figure 2.
Figure 2.. Heat map comparing PD-L1 SP263, SP142 and 22C3 antibody clones in urothelial carcinoma and hypopharyngeal squamous cell carcinoma.
Blue: PD-L1-positive tumors using established clinical algorithms as summarized in table 1. Orange: PD-L1-negative tumors.
Figure 3.
Figure 3.. Heat map comparing the performance betweeen E1L3N clone and other antibody clones.
Blue: PD-L1-positive tumors. Orange: PD-L1 negative tumors.
Figure 4.
Figure 4.. Scatterplots of pairwise comparison of tumor cell (TC, left) and immune cell (IC, right) percentage scoring between different antibody clones.
Blue: HP-SCC; green: UC. A 45-degree diagonal regression line indicated perfect correlation of TC scoring between the two antibody clones compared.
See this image and copyright information in PMC

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