J Breast Cancer.  2021 Jun;24(3):266-279. 10.4048/jbc.2021.24.e29.

Programmed Death Ligand 1 Immunohistochemistry in TripleNegative Breast Cancer: Evaluation of Inter-Pathologist Concordance and Inter-Assay Variability

Affiliations
  • 1Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
  • 2Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 3Department of Pathology, School of Medicine, Pusan National University, Busan, Korea
  • 4Department of Pathology, College of Medicine, Korea University, Seoul, Korea
  • 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
  • 6Department of Pathology, Chonnam National University Medical School, Gwangju, Korea
  • 7Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea
  • 8Department of Pathology, National Cancer Center, Goyang, Korea
  • 9Department of Pathology, Konkuk University School of Medicine, Seoul, Korea

Abstract

Purpose
The programmed death ligand 1 (PD-L1) SP142 assay with a 1% immune cell (IC) cutoff is approved for the selection of advanced triple-negative breast cancer (TNBC) patients for atezolizumab treatment. We aimed to evaluate the interobserver concordance of PD-L1 scoring and inter-assay variability of various PD-L1 assays in TNBC.
Methods
Thirty patients with primary TNBC were selected, and SP142, SP263, 22C3, and E1L3N assays were performed. PD-L1 staining in ICs and tumor cells (TCs) was scored by 10 pathologists who were blinded to the assay. The interobserver concordance among pathologists and the inter-assay variability of the four PD-L1 assays were analyzed. For SP142, the intraobserver concordance among the six pathologists was analyzed after training.
Results
The adjusted means of PD-L1 IC scoring ranged from 6.2% to 12.9% for the four assays; the intraclass correlations showed moderate (0.584–0.649) reader concordance. The PD-L1 IC scoring with a 1% cutoff resulted in identical scoring in 40.0%–66.7% of cases and a poor to moderate agreement (Fleiss κ statistic [FKS] = 0.345–0.534) for the four assays. The SP142 assay had the widest range of positive rate (56.5%–100.0%), lowest number of cases with identical scoring, and lowest FKS at 1% cutoff. Pairwise comparison of adjusted means showed significantly decreased PD-L1 staining in SP142 compared with the other assays in both ICs and TCs. As for the intraobserver concordance in the SP142 assay, the overall percent agreement was 87.8% with a 1% IC cutoff. After training, the proportion of cases with identical scoring at a 1% IC cutoff increased to 70.0%; the FKS also increased to 0.610.
Conclusion
The concordance of PD-L1 IC scoring among pathologists was low, at the 1% cutoff for the SP142 assay without training. SP142 showed the lowest PD-L1 expression in both IC and TC.

Keyword

B7-H1 antigen; Immune checkpoint inhibitors; Immunohistochemistry; Observer variation; Triple negative breast cancer
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