Abstract A046: CLDN18.2 Expression in PDAC: KRAS Independence and Stage IV Prognostic Value

作者：Salem Khoury, Ryan Lewis, Paul Roy, Saikat Chowdhury, Jarret Feldman, Brandon G. Smaglo, Robert A. Wolff, Shubham Pant, Jason Willis, Maria Pia Morelli, Ryan Huey, Micheal Overman, Huili Zhu, S Daniel Haldar, Camila Bragança Xavier, Nicole Balmaceda, Camila Lopez, Anthony Chen, Rebecca Snyder, Mathew H. G. Katz, Huamin Wang, Ethan B. Ludmir, Eugene J. Koay, John Paul Shen, Dan Zhao · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1557-3265.d32026-a046 · 研究领域：Medicine、Internal medicine、Oncology、Cancer research、Pathology

Abstract Background: In pancreatic adenocarcinoma (PDAC) management, KRAS inhibitors are entering into clinical use and claudin 18.2 (CLDN18.2) is an emerging therapeutic target. The expression levels of CLDN18.2 and KRAS mutation status and clinical outcome in PDAC is less studied. We would like to test the hypothesis of the relationship between CLDN18.2 expression levels with KRAS mutation status and CLDN18.2 association with survival. Methods: Retrospective analysis of 135 tumors from PDAC patients with CLDN18.2 tested by immunohistochemistry (IHC, clone 43-14A, Ventana) and KRAS mutation status at MD Anderson were analyzed. CLDN18.2 expression levels by IHC were calculated as % of cells with 2+/3+ membranous staining intensity. The Palantir Foundry system was used to query clinical and molecular information including overall survival (OS) data. Correlations of CLDN18.2 expression, KRAS mutation and OS were tested. Non-parametric tests were used given non-normal distributions of CLDN18.2 levels (Shapiro-Wilk p<0.001). Results: CLDN18.2 staining intensity was mostly 2+/3+ (n=90, 66.7%) and 3+ (n=9, 6.7%). CLDN18.2 prevalence was strongly cutoff-dependent: 40.5% at ≥75%, 59.1% at ≥40%, 71.0% at ≥10%, 73.3% at ≥1%. 122 (90.4%) patients were KRAS mutated and 13 were KRAS wildtype (9.6%). Median CLDN18.2 expression levels were 60% in KRAS-mutated tumors (n=119) versus 10% in KRAS-wildtype tumors (n=13, Mann-Whitney p=0.20). 44 patients were initially diagnosed with stage...