By Aurelia Noske, Daniel-Christoph Wagner, Kristina
Schwamborn, Sebastian Foersch, Katja Steiger, Marion Kiechle, Dirk Oettler,
Siranush Karapetyan, Alexander Hapfelmeier, Wilfried Roth, Wilko Weichert
The Breast: FULL LENGTH ARTICLE| VOLUME
60, P238-244, DECEMBER 01, 2021
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.
