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. 2022 Jul;25(4):741-750.
doi: 10.1007/s10120-022-01301-0. Epub 2022 Jun 4.

Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy

Joe Yeong #  1   2 , Huey Yew Jeffrey Lum #  3 , Chong Boon Teo #  4 , Benjamin Kye Jyn Tan  4 , Yiong Huak Chan  5 , Ryan Yong Kiat Tay  4 , Joan Rou-En Choo  6 , Anand D Jeyasekharan  6   7 , Qing Hao Miow  6 , Lit-Hsin Loo  8 , Wei Peng Yong #  6   7   9 , Raghav Sundar #  10   11   12   13   14
Affiliations

Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy

Joe Yeong et al. Gastric Cancer. 2022 Jul.

Abstract

Background: Immune checkpoint inhibitors (ICI) are now standard-of-care treatment for patients with metastatic gastric cancer (GC). To guide patient selection for ICI therapy, programmed death ligand-1 (PD-L1) biomarker expression is routinely assessed via immunohistochemistry (IHC). However, with an increasing number of approved ICIs, each paired with a different PD-L1 antibody IHC assay used in their respective landmark trials, there is an unmet clinical and logistical need for harmonization. We investigated the interchangeability between the Dako 22C3, Dako 28-8 and Ventana SP-142 assays in GC PD-L1 IHC.

Methods: In this cross-sectional study, we scored 362 GC samples for PD-L1 combined positive score (CPS), tumor proportion score (TPS) and immune cells (IC) using a multiplex immunohistochemistry/immunofluorescence technique. Samples were obtained via biopsy or resection of gastric cancer.

Results: The percentage of PD-L1-positive samples at clinically relevant CPS ≥ 1, ≥ 5 and ≥ 10 cut-offs for the 28-8 assay were approximately two-fold higher than that of the 22C3 (CPS ≥ 1: 70.3 vs 49.4%, p < 0.001; CPS ≥ 5: 29.1 vs 13.4%, p < 0.001; CPS ≥ 10: 13.7 vs 7.0%, p = 0.004). The mean CPS score on 28-8 assay was nearly double that of the 22C3 (6.39 ± 14.5 vs 3.46 ± 8.98, p < 0.001). At the clinically important CPS ≥ 5 cut-off, there was only moderate concordance between the 22C3 and 28-8 assays.

Conclusion: Our findings suggest that scoring PD-L1 CPS with the 28-8 assay may result in higher PD-L1 scores and higher proportion of PD-L1 positivity compared to 22C3 and other assays. Until stronger evidence of inter-assay concordance is found, we urge caution in treating the assays as equivalent.

Keywords: Biomarkers; Immune checkpoint inhibitors; Immunotherapy; Stomach neoplasms; Tumor.

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Conflict of interest statement

RS has received honoraria from Bristol-Myers Squibb, Lilly, Roche, Taiho, Astra Zeneca, DKSH and MSD; has advisory activity with Bristol-Myers Squibb, Merck, Eisai, Bayer, Taiho, Novartis, MSD and AstraZeneca; received research funding from MSD and Paxman Coolers; and has received travel grants from AstraZeneca, Eisai, Roche and Taiho Pharmaceutical. WPY has advisory activity with Abbvie, Amgen, AstraZeneca, BMS, Ipsen, Novartis, MSD; is a speaker with Bayer, Eisai, Lilly, Sanofi, Taiho. The rest of the authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Representative images of gastric cancer tissues stained using multiplex immunohistochemistry/immunofluorescence (mIHC/IF) [DAPI (Blue), PD-L1 22C3 (Magenta), PD-L1 SP142 (Yellow), PD-L1 28–8 (Green), CK (Red)]. (Magnification, 200×), from two different patients (A) and (B)
Fig. 2
Fig. 2
PD-L1 scoring obtained from 22C3, 28 to 8 and SP-142 assays. A Log-transformed violin plot of CPS scores on PD-L1 obtained from 22C3, 28 to 8 and SP-142 assays among the main cohort of gastric cancer patients (n = 344). B Heat map representation of correlation between PD-L1 scoring of CPS, TPS and IC obtained from 22C3, 28 to 8 and SP-142 assays among the main cohort of gastric cancer patients (n = 344). C Heat map representation of correlation between PD-L1 scoring of CPS, TPS and IC obtained from 22C3, 28 to 8 and SP-142 assays among the additional cohort of ICI-treated gastric cancer patients (n = 18)
See this image and copyright information in PMC

Comment in

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