Claudin 18.2 in cancer research and treatment: a pathologist's perspective

To provide a practical, pathology-centred overview of Claudin 18.2 as a biomarker and therapeutic target, covering biology, assay methods and interpretation, pre-analytical factors, clinicopathological associations and implications for treatment selection.

We performed a narrative review of the biomedical and pathology literature on CLDN18/Claudin 18.2, including basic science, translational studies, immunohistochemistry (IHC) and in situ assays, and clinical trials of Claudin 18.2-directed therapies. Reference lists were hand-searched to capture additional relevant reports. Emphasis was placed on data informing routine diagnostic practice (expression patterns, scoring, fixation variables, pitfalls).

Claudin 18.2 localises to tight junctions of differentiated gastric epithelium and is aberrantly expressed in gastric and gastro-oesophageal junction adenocarcinomas, with variable expression reported in pancreatic, biliary and other tumours. Loss or dysregulation of Claudin 18.2 contributes to tumour progression via disruption of epithelial integrity and activation of oncogenic pathways; infection-related and inflammation-related downregulation is described in gastric mucosa. For IHC, clone selection, tissue handling, fixation time and membrane-dominant scoring critically affect results; common pitfalls include cytoplasmic staining and heterogeneity. Claudin 18.2 expression shows predictive value for targeted agents under clinical use/evaluation, supporting its role as a companion biomarker. Reporting recommendations include membrane intensity/percentage thresholds and clear documentation of pre-analytical conditions.

Claudin 18.2 is a biologically plausible and clinically actionable biomarker. Robust pre-analytical handling, validated IHC protocols and standardised scoring are essential for reliable patient selection. Wider adoption of harmonised methods and further disease-specific studies will refine cut-offs, clarify prognostic value and optimise integration of Claudin 18.2-directed therapies into routine care.