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Updated: Jan 23, 2026

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Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled

Irene Coati1, Gábor Lotz2, Giuseppe Nicolò Fanelli1

  • 1Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.

British Journal of Cancer
|June 26, 2019
PubMed
Abstract

Insights

Claudin-18 (CLDN18) is frequently expressed in gastric and gastro-oesophageal cancers. Further research into CLDN18 heterogeneity is needed for clinical application in cancer treatment.

Area of Science:

  • Oncology
  • Gastroenterology
  • Molecular Biology

Background:

  • Claudin-18 (CLDN18) is a specific tight junction protein in gastric mucosa.
  • An isoform, Claudin 18.2, is a novel drug target for metastatic gastric cancer.

Purpose of the Study:

  • To investigate the immunohistochemical profile of CLDN18 and other biomarkers in gastric and gastro-oesophageal carcinomas.
  • To evaluate CLDN18 expression in primary tumors and matched nodal metastases.

Main Methods:

  • Immunohistochemistry was used to analyze CLDN18, p53, p16, E-cadherin, DNA mismatch repair proteins (MSH2, MSH6, MLH1, PSM2), HER2, and PDL-1.
  • Chromogenic in situ hybridization (CISH) assessed HER2 and Epstein-Barr virus (EBV)-encoded RNA (EBER).
  • A cohort of 523 primary gastric/gastro-oesophageal carcinomas and 135 matched metastases were analyzed.

Main Results:

  • High membranous CLDN18 expression was observed in 29.4% of primary tumors and 34.1% of metastases.
  • Abnormal CLDN18 expression (nuclear/cytoplasmic) occurred in 22.5% of primary tumors and 25.0% of metastases.
  • Significant CLDN18 intratumoral heterogeneity was found in 38.8% of cases. Positive CLDN18 expression correlated with non-antral GCs, Lauren diffuse type, and EBV-associated cancers.

Conclusions:

  • CLDN18 is frequently expressed in gastric and gastro-oesophageal cancers.
  • Further studies are required to determine the prognostic significance of CLDN18 heterogeneity.
  • Investigating CLDN18 heterogeneity is crucial for its implementation into clinical practice.

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