PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays

Samuel J Klempner ¹, Eric S Cowden ², Samuel L Cytryn ³

¹Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA.
²Novartis Pharmaceuticals Corporation, Cambridge, MA.
³Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
⁴Department of Medicine (DIMED), University of Padua and Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.
⁵Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
⁶Department of Surgery and Clinical Oncology, Toho University Graduate School of Medicine, Tokyo, Japan.
⁷Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
⁸Institute of Pathology, University Medical Center Mainz, Mainz, Germany.
⁹Department of Pathology, National Cancer Center, Tokyo, Japan.
¹⁰Novartis Pharmaceuticals Corporation, East Hanover, NJ.
¹¹University Clinic of Mainz, Mainz, Germany.

⁰Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA.

Jco Precision Oncology +

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June 1, 2024

View abstract on PubMed

Summary

Three PD-L1 assays show analytical concordance for gastric cancer testing using combined positive score (CPS) and tumor area positivity (TAP) algorithms. Digital image analysis confirmed technical performance, supporting assay flexibility.

Area Of Science

Oncology
Immunohistochemistry
Biomarker Analysis

Background

Clinical use of PD-L1 immunohistochemistry (IHC) in gastric cancer (GC) is complex due to multiple assays, scoring algorithms, and cutoffs.
Standardization is crucial for reliable PD-L1 expression assessment in GC treatment decisions.

Purpose Of The Study

To assess the analytical comparability of three commercially available PD-L1 IHC assays (28-8, 22C3, SP263).
To evaluate two scoring algorithms, combined positive score (CPS) and tumor area positivity (TAP), for PD-L1 assessment in GC.
To determine the concordance between different PD-L1 assays and scoring methods.

Main Methods

100 resected GC samples were stained using three PD-L1 assays.
Pathologists independently scored slides using CPS and TAP algorithms.
Statistical analyses, including Cohen's kappa and intraclass correlation, were performed.
Digital image analysis (DIA) was used to objectively evaluate assay performance.

Main Results

All three PD-L1 assays demonstrated comparable staining patterns in GC.
Reproducible PD-L1 positivity evaluations were observed despite intensity variations.
High inter- and intra-assay agreement (Cohen's kappa 0.47-1.00) was found for both CPS and TAP.
Excellent interpathologist concordance (ICC ≥0.92) and no significant difference in DIA performance were noted.

Conclusions

Significant analytical concordance exists between the three major PD-L1 assays when using TAP and CPS algorithms in GC.
Technical assay performance comparability is supported by DIA.
These findings support the flexible use of different PD-L1 assays and scoring algorithms for characterizing PD-L1 expression in GC.