Global Ring Study to Investigate the Comparability of Total Assay Performance of Commercial Claudin 18 Antibodies for Evaluation in Gastric Cancer

作者：Bharat Jasani, Philippe Tanière, Hans‐Ulrich Schildhaus, Kevin Blighe, Suzanne Parry, Dawn Wilkinson, Neil Atkey, Scott Clare-Antony, Clare McCabe, Christine M. Quinn, Steven Gibney, Andrew Dodson · 发表于：Laboratory Investigation · 年份：2023 · DOI：10.1016/j.labinv.2023.100284 · 被引用次数：22 · 研究领域：Gastric Cancer Management and Outcomes、HER2/EGFR in Cancer Research、Barrier Structure and Function Studies

Claudin 18.2 (CLDN18.2), the dominant isoform of CLDN18 in gastric tissues, is a highly specific tight junction protein of the gastric mucosa with variably retained expressions in gastric and gastroesophageal junction cancers. Additionally, CLDN18.2-targeted treatment with zolbetuximab, in combination with chemotherapy, has recently been assessed in 2 phase-III studies of patients with HER2-negative, locally advanced, unresectable, or metastatic gastric or gastroesophageal junction adenocarcinoma. These trials used the investigational VENTANA CLDN18 (43-14A) RxDx immunohistochemistry (IHC) assay on the Ventana BenchMark platform to identify patients eligible for CLDN18.2-targeted treatment. We report the findings of a global ring study evaluating the analytical comparability of concordance of the results of 3 CLDN18 antibodies (Ventana, LSBio, and Novus) stained on 3 IHC-staining platforms (Ventana, Dako, and Leica). A tissue microarray (TMA), comprising 15 gastric cancer cases, was stained by 27 laboratories across 11 countries. Each laboratory stained the TMAs using at least 2 of the 3 evaluated CLDN18 antibodies. Stained TMAs were assessed and scored using an agreed IHC-scoring algorithm, and the results were collated for statistical analysis. The data confirmed a high level of concordance for the VENTANA CLDN18 (43-14A; Ventana platform only) and LSBio antibodies on both the Dako and Leica platforms, with accuracy, precision, sensitivity, and specificity rates all reachin...