Getzenberg, Robert H.

Abstract Background: Pancreatic cancer is a frequently fatal disease that is often diagnosed at a late stage associated with a poor prognosis and an increasing impact on cancer related mortality. Despite advances, chemotherapy remains the mainstem of therapeutic interventions for this disease and most of the currently identified molecular alterations are not currently targetable. Therefore, novel biomarkers and strategies are necessary to impact patient outcomes. Claudin-18.2 (CLDN18.2) is a splice variant of the Claudin 18 family and is a component of tight junctions, which seal the paracellular spaces of epithelial and endothelial cells. CLDN18.2 is frequently retained in malignant gastric tissue and overexpressed in pancreatic and gastroesophageal adenocarcinomas. CLDN18.2 overexpression at the message and protein levels has been observed in pre-clinical studies involving pancreatic cancer cell lines and in tumors from pancreatic cancer patients. The goal of this study was to obtain a deeper understanding of CLDN18.2 positivity and CLDN18.2 expression and the associated clinical prevalence, prognostic implications, patient clinical characteristics and relationship with other biomarkers in pancreatic ductal adenocarcinoma (PDAC) patient samples. Design: This was a single institution/reference laboratory based retrospective study including as many as 320 patients, in which CLDN18.2 positivity as defined by ≥ 75% of the tumor cells expressing moderate to strong membranous staining was examined. The goals were to evaluate CLDN18.2 in tumor samples by immunohistochemistry for prevalence in pancreatic adenocarcinoma patients. Claudin 18.2 expression was assessed by the Ventana (43-14A) Class I IVD that was purchased from Ventana/Roche Diagnostics. In addition to prevalence, CLDN18.2 was evaluated with respect to the clinicopathological features of patients, patient prognosis, adjusted for clinical covariables, response to treatments and relationship to patient demographics, tumor grade and disease status. Patient information has been obtained from electronic medical records and research database to establish clinical course (survival status, metastatic sites, etc.) along with patient demographics. Conclusions: CLDN18.2 is a novel potentially actionable biomarker in patients with advanced and metastatic pancreatic adenocarcinoma. This study provides important clinical information regarding CLDN18.2 expression in these patients that is important to consider when evaluating biomarkers in these patients. Funding for the study was provided by Astellas Pharma Global Development, Inc. Citation Format: Allison Kerper, Robert H. Getzenberg, Rondell P. Graham. Real world clinical characteristics of claudin 18.2 expression in patients with pancreatic adenocarcinoma [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 5915.