Abstract 2141: Claudin 18.2 (CLDN18.2) expression prevalence, prognostication and clinical variables in gastric and gastroesophageal junction adenocarcinoma patient samples
Authors: Sewastjanow Matheus , Yamashita Kohei , Iwata Kenneth K. , Moran Diarmuid , Elsouda Dina , Pizzi Melissa , Vicentini Ernesto Rosa , Shanbhag Namita , Ta Anh , Waters Rebecca , Chatterjee Deyali , Ajani Jaffer 
Published: April 2023

Introduction: CLDN18.2 is an isoform of CLDN18, a member of the Claudin family of proteins with expression that is highly restricted to the gastric epithelium of normal gastric tissue. In tumor tissue from patients with gastric (G) and gastroesophageal junction (GEJ) adenocarcinoma, CLDN18.2 expression has been found to be frequently expressed as determined by gene expression and immunohistochemistry (IHC). Based on its expression pattern in malignant tissues and past clinical studies, CLDN18.2 has emerged as a target of interest for new therapeutics. The goal of this study was to obtain a deeper understanding of CLDN18.2 expression, prevalence, as well as its prognostic implications, clinical characteristics, and relationship with select biomarkers in G and GEJ adenocarcinoma patient samples.

Methods: Formalin-Fixed Paraffin-Embedded tissue samples of G and GEJ adenocarcinoma patients (n=304) from a tissue biorepository at MD Anderson Cancer Center were retrospectively studied for CLDN18.2 expression by IHC (antibody clone 43-14A). Tissue samples included primary G and GEJ adenocarcinoma tissues, matched pre- and post- metastatic samples and matched naïve versus chemotherapy treated patients. Interpretation of CLDN18.2 expression was conducted by clinical pathologists to score samples based on staining intensity (≥2+) as well as the percentage of positively stained CLDN18.2 tumor cells (≥75% and ≥50%). CLDN18.2 expression was analyzed for its association with prognosis, clinical and demographic data and its relationship with other variables (e.g. sex, age, histology, HER2, PD-L1, EBV).

Results: Prevalence of CLDN18.2 expression at the &gt;75% cutoff was observed in 51% and 35% of samples from G and GEJ adenocarcinoma patients, respectively, with a combined prevalence of 44%. At the &gt;50% cutoff, CLDN18.2 was expressed in 64% and 45% of G and GEJ adenocarcinoma samples, respectively, with a combined prevalence of 56%. CLDN18.2 expression did not appear to associate with prognosis at either CLDN18.2 expression cutoff. Associations between CLDN18.2 expression based upon sex, tumor grade, histology, peritoneal metastasis and signet ring morphology were observed. When evaluating the relationship between CLDN18.2 expression (at either cutoff) and other select biomarkers (MSI, PD-L1, HER2 and EBV), data suggests there is limited overlap.

Conclusion: Based upon the data from this study, CLDN18.2 appears to be a highly prevalent, but not prognostically associated biomarker in G and GEJ adenocarcinoma patients. Additionally, CLDN18.2 expression appears independent of other biomarkers, however further research is warranted. These data are consistent with prior reports and support CLDN18.2 as a promising molecular target for therapeutics to treat G and GEJ adenocarcinoma patients.

Citation Format: Matheus Sewastjanow, Kohei Yamashita, Kenneth K. Iwata, Diarmuid Moran, Dina Elsouda, Melissa Pizzi, Ernesto Rosa Vicentini, Namita Shanbhag, Anh Ta, Rebecca Waters, Deyali Chatterjee, Jaffer Ajani. Claudin 18.2 (CLDN18.2) expression prevalence, prognostication and clinical variables in gastric and gastroesophageal junction adenocarcinoma patient samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2141.