Abstract 681: A novel approach of Claudin 18 immunohistochemistry testing demonstrated comparable performance and high concordance compared to Ventana 43-14A in gastric cancer

Abstract Background: Claudin(CLND)18 is a tight-junction molecule consisting two Isoforms:CLND18.1 and CLND18.2. Isofrom CLND18.2 is specificly expressed in gastric cancer. Zolbetuximab is the first CLDN18.2 therapeutic monoclonal antibody approved by FDA. VENTANA® CLND18(43-14A), a pan-CLND18 immunohistochemistry (IHC) testing, was approved as companion diagnostics simutanusly. Validation between different Claudin 18 IHC testing approaches could improve the convenience of diagnostics in clinical use. Methods: A total of 68 gastric cancer samples were enrolled in this study. Expressing status of Claudin 18 was evaluated independently by two IHC approaches. AmoyDx CLDN18 (43-14A) assay was used as testing reagent and VENTANA® CLDN18 (43-14A) RxDx acts as reference reagent. Claudin 18 positive was defined as: tumor with staining intensity of 2+ or 3+(total) in ≥75% of tumor cell. Results: Validtaion results was shown in Table 1. 21 positive cases and 47 negative cases were identified by two reagents. Standing for a 100%(84.54% - 100%) positive percent agreement (PPA), 100% (92.44% - 100%) negative percent agreement (NPA), and 100% (94.65% - 100%) overall percent agreement (OPA). Poisson distribution analysis of the proportion of cells with four staining intensities(3+, 2+, 1+ and 0) demostrated that the staining intensity of the two approaches was highly consistent (R = 0.99-1, p < 2.26e-16). When the positive threshold was exploratively adjusted ( 2+/3+ cells ≥50%), high concordance was still maintained (PPA 100%, NPA 93.55%, OPA 97.06%, Table 1.) except 2 conflict samples, which were close to the exploratively threshold. Conclusion: Two Claudin 18 testing approaches demonstrated high concordance. It has potential versatility in future clinical practice. Citation Format: Zhenghua Tang, peng cheng, Xin Liu, Huangbin Lu, Jingjing Xu, Yiling Cai, Changbin Zhu. A novel approach of Claudin 18 immunohistochemistry testing demonstrated comparable performance and high concordance compared to Ventana 43-14A in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 681.