ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2025
Claudin 18.2 Expression in 1404 Digestive Tract Adenocarcinomas Including 1175 Colorectal Carcinomas: Distinct Colorectal Carcinoma Subtypes Are Claudin 18.2 Positive.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Retrospective analysis of Claudin 18.2 expression in 64 patients with advanced gastrointestinal peritoneal disease: a potential therapeutic target for high-grade appendiceal mucinous carcinoma.Journal of clinical pathology · 2026Article
- Article
- Histological and biomarker landscape of Claudin18.2-positive gastric and gastroesophageal junction cancers: a study of 937 cases.Virchows Archiv : an international journal of pathology · 2026Article
- Utility of quantitative pathologic analysis of pT1 colorectal carcinomas to improve prediction of lymph node metastasis.Virchows Archiv : an international journal of pathology · 2026Article
- Claudin proteins as emerging therapeutic targets for solid tumours.Nature reviews. Cancer · 2026Review
- Claudin18.2 positive gastric cancer: biology, tumor microenvironment, and therapeutic strategies.Journal of hematology & oncology · 2026Review
- Resistance mechanisms and countermeasures in CLDN18.2-positive tumors: from molecular networks to clinical practice.Frontiers in oncology · 2026Review
- Next-generation CAR-T engineering for colorectal cancer: integrating targets, tumor microenvironment barriers, and emerging strategies.Frontiers in immunology · 2026Review
- Precision Antibody Therapy in Gastric and Gastroesophageal Cancer: Targeting FGFR2b, CLDN18.2, and VEGFR2.Cells · 2025Review
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7 authors.
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Abstract
Claudin 18.2 (CLDN18.2) immunohistochemical (IHC) expression can be used to select patients with gastric/gastroesophageal junction adenocarcinomas for zolbetuximab (IMAB362) therapy, zolbetuximab (IMAB362) being a monoclonal antibody targeting CLDN18.2. The aim of this study was to correlate IHC expression of CLDN18.2 with clinicopathologic and molecular features in a large series of digestive tract cancers. IHC for CLDN18.2 was performed on tissue microarrays from 1404 adenocarcinomas including 155 gastric/gastroesophageal, 74 pancreatic ductal, and 1175 colorectal (576 in the initial test cohort; 599 in the subsequent validation cohort), and correlated with HER2 and mismatch repair (MMR) status. Cases were scored as CLDN18.2 positive or negative, with positivity defined as moderate-to-strong membranous staining in ≥75% of tumor cells. CLDN18.2 expression was correlated with clinicopathologic and molecular features for all colorectal adenocarcinomas. CLDN18.2 was positive in 39% (61/155) of gastric/gastroesophageal adenocarcinomas, 38% (28/74) of pancreatic ductal adenocarcinomas, and 3.4% (40/1175) of colorectal adenocarcinomas (P < .001). For gastric/gastroesophageal and pancreatic ductal adenocarcinoma, there was no correlation between CLDN18.2 expression and either HER2 or MMR status. In contrast, CLDN18.2-positive colorectal adenocarcinomas had distinct clinicopathologic and molecular features. CLDN18.2-positive colorectal adenocarcinomas were more frequently proximally located and were more often MMR deficient and BRAF V600E positive (all with P < .05). Quantitative pathologic analysis using the digital pathology biomarker QuantCRC (Aiforia) demonstrated marked differences in histologic features between CLDN18.2-positive and CLDN18.2-negative colorectal adenocarcinomas, with CLDN18.2-positive tumors having an increased tumor:stroma ratio and %mucin but decreased %immature stroma in both the test and validation cohorts (all with P < .05). In conclusion, CLDN18.2-positive colorectal adenocarcinomas are frequently MMR deficient and BRAF V600E mutated, and demonstrate distinct histologic features. Future studies addressing the efficacy of zolbetuximab therapy in this subset of colorectal cancers are needed.
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