Indirect Clinical Validation of a Programmed Death-Ligand 1 Laboratory-Developed Test for Gastric/Gastroesophageal Junction Adenocarcinoma with 22C3 Antibody Concentrate

Ji Min Kim, Binnari Kim, Eunji Kim, Minsun Jang, Jun Hun Cho, Hye Seung Lee, Yoonjin Kwak, Lingkang Huang, Radha Krishnan, Sally Y. Bai, Mounia Mounawar, Kyoung Mee Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The PD-L1 IHC 22C3 pharmDx used on the Dako Autostainer Link 48 (ASL48) staining platform is an established method for assessing programmed death-ligand 1 (PD-L1) expression in tumor tissue and determining patient eligibility for pembrolizumab treatment; however, the availability of this platform is limited in Europe and Asia. Objectives: The aims of this study were to develop and optimize protocols for the PD-L1 22C3 antibody concentrate with multiple immunohistochemistry staining platforms and to validate these protocols using PD-L1 combined positive score (CPS) with a cut-off of ≥ 1 in gastric or gastroesophageal junction adenocarcinoma. Design: The 22C3 antibody concentrate was tested and optimized protocols were developed for use with three staining platforms: Dako ASL48, Ventana BenchMark ULTRA, and Leica BOND-MAX. Tumor specimens (N = 120) from patients with gastric or gastroesophageal junction adenocarcinoma were used for the validation study; these specimens were evaluated independently by three pathologists for PD-L1 CPS as a continuous variable and using a cut-off of ≥ 1. PD-L1 IHC 22C3 pharmDx used on the Dako ASL48 platform served as the reference or gold standard. Results: The intraclass correlation coefficient of CPS as a continuous variable between the gold standard and each staining platform assessed was 0.910–0.989. When CPS was dichotomized based on a cut-off of ≥ 1, depending on the pathologist and the platform used, positive percentage agreement was 81–99% and negative percentage agreement was 90–100%. Interobserver agreement using the gold standard showed substantial agreement (κ = 0.779). Conclusion: The PD-L1 22C3 antibody concentrate can potentially be used with the laboratory-developed test on three commercially available immunohistochemistry staining platforms to determine PD-L1 expression in tumor samples from patients with gastric or gastroesophageal junction adenocarcinoma.

Original languageEnglish
Pages (from-to)679-688
Number of pages10
JournalMolecular Diagnosis and Therapy
Volume26
Issue number6
DOIs
StatePublished - Nov 2022

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