Reproducibility and concordance of 4 clinically developed programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays in triple-negative breast cancer (TNBC)
Noske A.1, Ammann J.2, Wagner D.-C.3, Denkert C.4, Lebeau A.5,6, Sinn P.7, Kreipe H.-H.8, Baretton G.9, Steiger K.1, Kiechle M.10, Hieke-Schulz S.2, Roth W.3, Weichert W.1
1Pathologie TU München, München, Deutschland, 2Roche Pharma AG, Grenzach-Wyhlen, Deutschland, 3Pathologie Johannes Gutenberg-Universität, Mainz, Deutschland, 4Pathologie Philipps-Universität, Marburg, Deutschland, 5Pathologie Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland, 6Gemeinschaftspraxis für Pathologie, Lübeck, Deutschland, 7Pathologie Universitätsklinik Heidelberg, Heidelberg, Deutschland, 8Pathologie Medizinische Hochschule Hannover, Hannover, Deutschland, 9Pathologie Universitätsklinikum Carl Gusatv Carus Dresden, Dresden, Deutschland, 10Klinikum rechts der Isar, Technische Universität München, München, Deutschland
Background: Atezolizumab (an anti-PD-L1 antibody) has shown clinical activity in patients with metastatic TNBC who have PD-L1 expression on tumour-infiltrating immune cells (IC). We analysed the performance of 4 PD-L1 IHC assays for PD-L1 IC expression in TNBC.
Methods: Thirty TNBC specimens were selected from a set of 107 based on PD-L1 IC expression per VENTANA SP142, to represent the distribution of PD-L1 IC-positivity in the pivotal atezolizumab studies. Serial histologic sections were stained with VENTANA SP142 and SP263, and DAKO 22C3 and 28-8, per manufacturer protocols. Slides were blinded for both assay and sample information and scored by trained readers at 7 sites for PD-L1 IC expression (% per tumour area), by online virtual microscopy.
Results: Adjusted means of PD-L1 IC staining ranged from 3.7% to 7.8%; SP263 stained more IC than the other assays. Pairwise comparison of adjusted means showed small, non-significant differences (-1.2% to 0.6%) between SP142, 22C3 and 28-8, but a significant increase in PD-L1 staining for SP263 vs. the other assays (3.0% to 4.2%). Intra-class correlations for the assays showed moderate (0.460) to excellent (0.805) reader concordance.
Conclusions: This first multicentre analytical PD-L1 assay comparison study in TNBC indicates good-to-high reproducibility and concordance of PD-L1 IC expression between the SP142, 22C3 and 28-8 assays, while higher expression was detected with SP263. Hence, SP142, 22C3 and 28-8 may be considered analytically interchangeable for PD-L1 IC testing.
Previously presented at ESMO 2019, 359P, Abstract Noske A et al. - Reused with permission.