Interassay and interobserver comparability study of four programmed death-ligand 1 (PD-L1) immunohistochemistry assays in triple-negative breast cancer.

Different immunohistochemical programmed death-ligand 1 (PD-L1) assays and scorings have been reported to yield variable results in triple-negative breast cancer (TNBC). We compared the analytical concordance and reproducibility of four clinically relevant PD-L1 assays assessing immune cell (IC) score, tumor proportion score (TPS), and combined positive score (CPS) in TNBC. Primary TNBC resection specimens (n = 104) were stained for PD-L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3, and DAKO 28-8. PD-L1 expression was scored according to guidelines on virtual whole slide images by four trained readers. The mean PD-L1 positivity at IC-score ≥1% and CPS ≥1 ranged between 53% and 75% with the highest positivity for SP263 and comparable levels for 22C3, 28-8, and SP142. Inter-assay agreement was good between 28-8 and 22C3 across all scores and cut-offs (kappa 0.68-0.74) and for both assays with SP142 at IC-score ≥1% and CPS ≥1 (kappa 0.61-0.67). The agreement between SP263 and all other assays was substantially lower for all scores. Inter-reader agreement for each assay was good to excellent for IC-score ≥1% (kappa 0.73-0.78) and CPS ≥1 (kappa 0.68-0.74), fair to good for CPS ≥10 (kappa 0.52-0.67) and TPS ≥1% (kappa 0.53-0.72). The percentage of overlapping cases in the positive/negative category was >90% between IC-score ≥1% and CPS ≥1 but below when comparing IC-score ≥1% with CPS ≥10. We demonstrate an overall good inter-reader agreement for all PD-L1 assays in TNBC along with assay specific differences in positivity and concordances, which may aid to select the right test strategy in routine diagnostics.
Competing Interests: Declaration of competing interest AN has attended Advisory Boards. DCW has received funding from Roche Pharma AG, BMS, and MSD. KSc has attended Advisory Boards and served as a speaker for Roche, MSD, and BMS. KS has received funding from Roche Pharma AG. MK has received remuneration from Springer Press, Biermann Press, Celgene, AstraZeneca, Myriad Genetics and Teva, received consultancy or advisory fees from Myriad Genetics, KVB, DKMS LIFE, BLÄK and TEVA, holds stock in Therawis Diagnostics GmbH and AIM GmbH and received funding from Sphingotec, Deutsche Krebshilfe, DFG, BMBF, the Senator Roesner Foundation and the Dr Pommer-Jung Foundation. DO is an employee of MSD Sharp & Dohme GmbH. WR has received funding from Roche Pharma AG, has attended Advisory Boards and served as a speaker for Roche, MSD, Novartis. WW has attended Advisory Boards, served as speaker for Roche, MSD, BMS, AstraZeneca, Pfizer, Merck, Lilly, Boehringer, Novartis, Takeda, Bayer, Amgen, Astellas, Illumina, Siemens, Agilent and Molecular Health and receives research funding from Roche, MSD, BMS and AstraZeneca. The remaining authors (SF, SK, AH) have no conflict of interest.
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