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Aims: The aim of this multicentre study was to harmonize programmed death‐ligand 1 (PD‐L1) immunohistochemistry (IHC) and melanoma scoring. To provide a reference for PD‐L1 expression independently of the IHC protocol, PD‐L1 mRNA expression was compared with IHC. Methods and results: Standardized PD‐L1 assays (22C3, 28–8, SP142, SP263) and laboratory‐developed tests (QR1, 22C3) were evaluated on three IHC platforms with a training set (seven cases). mRNA expression was determined by RNAscope (CD274/PD‐L1 probe) and analysed with image analysis. PD‐L1 IHC findings were scored by seven blinded pathologists using the tumour proportion score (TPS), the combined positive score (CPS), and the MELscore. This method was validated by three blinded pathologists on 40 metastatic melanomas. Concordances among various antibody/platforms were high across antibodies [intraclass correlation coefficient (ICC) >0.80 for the CPS], except for SP142. Two levels of immunostaining intensity were observed: high (QR1 and SP263) and low (28–8, 22C3, and SP142). Reproducibilities across pathologists were higher for QR1 and SP263 (ICC ≥0.87 and ICC ≥0.85 for the TPS and the CPS, respectively). QR1, SP263 and 28–8 showed the highest concordance with mRNA expression. We developed a standardized method for PD‐L1 immunodetection and scoring, tested on 40 metastatic melanomas. Concordances among antibodies were excellent for all criteria, and concordances among pathologists were better for the MELscore than for other scores. Conclusion: Harmonization of PD‐L1 staining and scoring in melanomas with good concordance is achievable with the PD‐L1 IHC protocols applied to other cancers; this reproducible approach can simplify daily practice. [ABSTRACT FROM AUTHOR]

Aims: Studies in various cancer types have demonstrated discordance between results from different programmed death‐ligand 1 (PD‐L1) assays. Here, we compare the reproducibility and analytical concordance of four clinically developed assays for assessing PD‐L1‐positivity in tumour‐infiltrating immune cells in the tumour area (PD‐L1‐IC‐positivity) in triple‐negative breast cancer (TNBC). Methods and results: Primary TNBC resection specimens (n = 30) were selected based on their PD‐L1‐IC‐positivity per VENTANA SP142 (<1%: 15 cases; 1–5%: seven cases; >5%: eight cases). Serial histological sections were stained for PD‐L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3 and DAKO 28‐8. PD‐L1‐IC‐positivity and tumour cell expression (≥1 versus <1%) were scored by trained readers from seven sites using online virtual microscopy. The adjusted mean of PD‐L1‐IC‐positivity for SP263 (7.8%) was significantly higher than those for the other three assays (3.7–4.9%). Differences in adjusted means were statistically significant between SP263 and the other three assays (P < 0.0001) but not between the three remaining assays when excluding SP263 (P = 0.0961–0.6522). Intra‐class correlation coefficients revealed moderate‐to‐strong inter‐reader agreement for each assay (0.460–0.805) and poor‐to‐strong inter‐assay agreement for each reader (0.298–0.678) on PD‐L1‐IC‐positivity. Conclusions: In this first multicentre study of different PD‐L1 assays in TNBC, we show that PD‐L1‐IC‐positivity for SP142, 22C3 and 28‐8 was reproducible and analytically concordant, indicating that these three assays may be analytically interchangeable. The relevance of the higher PD‐L1‐IC‐positivity for SP263 should be further investigated. [ABSTRACT FROM AUTHOR]