ArticleVirchows Archiv : an international journal of pathology2026
Histological and biomarker landscape of Claudin18.2-positive gastric and gastroesophageal junction cancers: a study of 937 cases.
Article in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Unveiling the molecular profile of adenosquamous gallbladder carcinoma: characterization of a Caucasian cohort.Histopathology · 2026Article
- Resistance mechanisms and countermeasures in CLDN18.2-positive tumors: from molecular networks to clinical practice.Frontiers in oncology · 2026Review
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9 authors.
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Abstract
Although Claudin18.2 (CLDN18.2) is a promising therapeutic target in gastric and gastroesophageal junction cancer (G/GEJ), its expression profile based on histological subtypes remains unclear. This study aimed to investigate CLDN18.2 expression across various histological subtypes and its associations with clinicopathological features and crucial biomarkers. Tissue sample from 937 patients with G/GEJ was collected. Immunohistochemistry for CLDN18 (43-14A), PD-L1, HER2, and MMR proteins was performed on whole-section slides. EBER was detected by in situ hybridization. The overall positivity rate of CLDN18.2 was 25.8% (242/937). The highest CLDN18.2 positivity rate was observed in adenocarcinoma (AC) at 32.9% (211/641), followed by neuroendocrine neoplasms (NENs) at 12.8% (28/218), with a lower rate in adenosquamous carcinoma (ASC) at 6.3% (3/48), but CLDN18.2 was negative in squamous cell carcinoma (SCC) and undifferentiated carcinoma (P < 0.001). Analysis of AC histomorphology revealed that the highest positivity rate was observed in gastric carcinoma with lymphoid stroma (83.3%), whereas mucinous and hepatoid adenocarcinoma showed lower positivity rates (10.0% and 11.5%, P < 0.001). In ASC, the squamous component demonstrated CLDN18.2 expression in one case, which was characterized by EBV positivity and extensive stromal lymphocytic infiltration. In AC, CLDN18.2 positivity was significantly higher in EBV-positive compared to EBV-negative tumors (70.2% vs. 29.4%, P < 0.001). CLDN18.2 was not significantly associated with PD-L1 or HER2 status regardless of histological subtype (P > 0.05). This study characterized the histological profile of CLDN18.2-positive G/GEJ and broadened our understanding of subgroups likely to benefit from CLDN18.2-targeted therapy.
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