Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas

Simple Summary: Claudin-18 is a tight junction protein expressed in various cancer types including gastric and gastroesophageal junction cancer. The claudin-18.2 isoform represents a promising target for novel experimental drugs such as zolbetuximab (IMAB362), currently under investigation in several clinical trials of advanced gastrointestinal tumors. In this study, we aim to evaluate the immunohistochemical profile of CLDN18 in a real-world and mono-institutional series of gastric and gastroesophageal carcinomas. The association of CLDN18 expression with clinicopathological features and survival outcomes was investigated.The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominant isoform of CLDN18 in normal gastric and gastric cancer tissues. In this work, we evaluated the immunohistochemical (IHC) profile of CLDN18 and its correlation with clinical and histopathological features including p53, E-cadherin, MSH2, MSH6, MLH1, PMS2, HER2, EBER and PD-L1 combined positive score, in a large real-world and mono-institutional series of advanced GCs (n = 280) and GECs (n = 70). The association of IHC results with survival outcomes was also investigated. High membranous CLDN18 expression (2+ and 3+ intensity & GE;75%) was found in 117/350 (33.4%) samples analyzed. CLDN18 expression correlated with age < 70 (p = 0.0035), positive EBV status (p = 0.002), high stage (III, IV) at diagnosis (p = 0.003), peritoneal involvement (p < 0.001) and lower incidence of liver metastases (p = 0.013). CLDN18 did not correlate with overall survival. The predictive value of response of CLDN18 to targeted agents is under investigation in several clinical trials and further studies will be needed to select patients who could benefit from these therapies.

Automated summary

This study evaluated the immunohistochemical profile of CLDN18 and its association with clinicopathological features and survival outcomes in gastric and gastroesophageal carcinomas. High membranous CLDN18 expression was found in a significant portion of samples, and correlated with certain clinical characteristics but not overall survival. Further studies are needed to determine the predictive value of CLDN18 expression in response to targeted agents.