Inter-Rater Agreement in PD-L1 (22C3) Expression Evaluation in Colon Cancer
5 affiliations
- 1Department of Pathology, Zealand University Hospital, Roskilde
- 2Center for Surgical Science, Department of Surgery, Zealand University Hospital, Køge
- 3Department of Pathology, Rigshospitalet, Copenhagen
- 4Visiopharm A/S, Hoersholm
- 5Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Abstract
Programmed death-ligand 1 (PD-L1) is a predictive biomarker in various cancers. In colorectal cancer, PD-L1 expression evaluation is not part of the routine examination and standardized evaluation methods are lacking. This study aimed to examine inter-rater agreement in PD-L1 expression evaluation in patients with colon cancer (CC) using different manual scoring methods, and to compare the manual methods to a digital evaluation. Two pathologists evaluated 188 PD-L1-stained slides from patients with CC. The tumor proportion score (TPS) and immune cell score (ICS) were categorized as <1%, 1-9%, and ≥10% positivity and the combined positive score (CPS) as <1, 1-9, and ≥10 positivity. Inter-rater agreement was assessed using different cutoffs and consensus scores were compared with an in-house-developed digital algorithm quantifying PD-L1. Percentage agreement was 98.9% for TPS, 85.6% for ICS, and 88.8% for CPS. When dichotomized using 1% or 10% for ICS and 1 or 10 for CPS as cutoffs, the percentage agreement increased. Only 2 cases presented with a consensus TPS ≥1%, while 96.8% had a consensus ICS of <10%, and 98.4% a consensus CPS of <10. When the digital PD-L1 score was categorized into low and high, the highest agreement with the manual evaluations was reached using the third quartile as a cutoff. Conclusively, high inter-rater percentage agreements were obtained for all scoring methods, although kappa values varied. Results comparable to the manual evaluation were reached with a digital algorithm. A digital approach can potentially eliminate inter-rater variability. Clinically relevant cutoff values remain to be determined.
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BibTeX
@article{jepsen2026interrater,
title = {{Inter-Rater Agreement in PD-L1 (22C3) Expression Evaluation in Colon Cancer}},
author = {Dea N.M. Jepsen and Marianne B. Jensen and Trine L. Grantzau and Astrid L.B. Bennedsen and Thomas T. Eriksen and Michael Bzorek and Ismail Gögenur and Anne-Marie K. Fiehn},
journal = {Applied Immunohistochemistry \& Molecular Morphology},
year = {2026},
month = aug,
doi = {10.1097/pai.0000000000001345},
url = {https://doi.org/10.1097/pai.0000000000001345},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Inter-Rater Agreement in PD-L1 (22C3) Expression Evaluation in Colon Cancer
AU - Dea N.M. Jepsen
AU - Marianne B. Jensen
AU - Trine L. Grantzau
AU - Astrid L.B. Bennedsen
AU - Thomas T. Eriksen
AU - Michael Bzorek
AU - Ismail Gögenur
AU - Anne-Marie K. Fiehn
PY - 2026
DA - 2026/08/17
JO - Applied Immunohistochemistry & Molecular Morphology
DO - 10.1097/pai.0000000000001345
UR - https://doi.org/10.1097/pai.0000000000001345
AB - Programmed death-ligand 1 (PD-L1) is a predictive biomarker in various cancers. In colorectal cancer, PD-L1 expression evaluation is not part of the routine examination and standardized evaluation methods are lacking. This study aimed to examine inter-rater agreement in PD-L1 expression evaluation in patients with colon cancer (CC) using different manual scoring methods, and to compare the manual methods to a digital evaluation. Two pathologists evaluated 188 PD-L1-stained slides from patients with CC. The tumor proportion score (TPS) and immune cell score (ICS) were categorized as <1%, 1-9%, and ≥10% positivity and the combined positive score (CPS) as <1, 1-9, and ≥10 positivity. Inter-rater agreement was assessed using different cutoffs and consensus scores were compared with an in-house-developed digital algorithm quantifying PD-L1. Percentage agreement was 98.9% for TPS, 85.6% for ICS, and 88.8% for CPS. When dichotomized using 1% or 10% for ICS and 1 or 10 for CPS as cutoffs, the percentage agreement increased. Only 2 cases presented with a consensus TPS ≥1%, while 96.8% had a consensus ICS of <10%, and 98.4% a consensus CPS of <10. When the digital PD-L1 score was categorized into low and high, the highest agreement with the manual evaluations was reached using the third quartile as a cutoff. Conclusively, high inter-rater percentage agreements were obtained for all scoring methods, although kappa values varied. Results comparable to the manual evaluation were reached with a digital algorithm. A digital approach can potentially eliminate inter-rater variability. Clinically relevant cutoff values remain to be determined.
SN - 1541-2016
SN - 1533-4058
ER -