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High fidelity of Claudin-18.2 expression in primary and matched metastatic (lymph nodes, peritoneum, and liver)

Carlotta Franzina1, Michele Bevere2, Samantha Bersani1

  • 1Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy.

Human Pathology
|December 13, 2025
PubMed
Summary

Claudin-18.2 (CLDN18.2) is expressed in pancreatic cancer. This study found high concordance of CLDN18.2 expression between primary tumors and metastases, supporting anti-CLDN18.2 therapies for pancreatic ductal adenocarcinoma.

Keywords:
CLDN18CLDN18.2ClaudinMetastasesMetastasisPDACPancreatic cancer

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Area of Science:

  • Oncology
  • Molecular Pathology

Background:

  • Claudin-18.2 (CLDN18.2) is a tight-junction protein found in various cancers, including pancreatic ductal adenocarcinoma (PDAC).
  • Targeted therapies against CLDN18.2 are approved for gastric cancer and under investigation for PDAC.

Purpose of the Study:

  • To determine CLDN18.2 expression patterns in primary PDAC and matched metastatic sites.
  • To assess the concordance rate of CLDN18.2 positivity between primary PDAC and its metastases.

Main Methods:

  • Whole-slide immunohistochemistry was used to evaluate CLDN18.2 expression in primary PDAC and matched lymph node, peritoneal, and liver metastases.
  • Expression was quantified by cell percentage and staining intensity (H-score).
  • Tumor positivity was defined as ≥75% of tumor cells with 2+/3+ staining.

Main Results:

  • The study analyzed 20 PDAC/lymph node metastases, 30 PDAC/peritoneal metastases, and 12 PDAC/liver metastases cohorts.
  • Mean CLDN18.2 positivity varied across primary tumors (46.5%) and metastases (LNM: 60%, PM: 31%, LIVM: 22%).
  • High concordance rates were observed: 70.0% for PDAC/LNM, 93.3% for PDAC/PM, and 100.0% for PDAC/LIVM.

Conclusions:

  • There is a high correspondence of CLDN18.2 positivity between primary PDAC and matched metastatic sites.
  • These findings provide a strong rationale for investigating anti-CLDN18.2 therapeutic strategies in PDAC.