Expression of CLDN18.2 in Invasive Mucinous Adenocarcinomas of the Lung

Background/Aim: Invasive mucinous adenocarcinoma (IMA) of the lung is a rare adenocarcinoma subtype with abundant intracytoplasmic mucin and poor response to standard non-small cell lung cancer chemotherapy. Molecularly targeted therapies may be useful in IMA. Zolbetuximab is a chimeric IgG1 monoclonal antibody against Claudin-18.2 (CLDN18.2) that induces cell death in CLDN18.2-positive gastric and gastro-esophageal junction adenocarcinomas. If lung IMAs also highly express CLDN18.2, they may be candidates for zolbetuximab treatment. This study evaluated CLDN18.2 expression in lung IMAs by immunohistochemistry. Materials and Methods: We analyzed surgically resected samples comprising 30 IMAs, 10 non-mucinous adenocarcinomas (NMAs), 10 squamous cell carcinomas (SqCCs), 10 small cell carcinomas (SmCCs), 9 large cell carcinomas (LCCs), and 10 large cell neuroendocrine carcinomas (LCNECs) of the lung. Results: We confirmed CLDN18.2 expression (H-score ≥50 points) in 77% of IMA samples. Its expression was rarely observed in other histological types of lung cancer. Conclusion: CLDN18.2 is frequently expressed in IMAs but rarely in other major lung cancer subtypes, suggesting that zolbetuximab may represent a promising targeted therapy for IMA.