Claudin-18.2 Immunohistochemical Evaluation in Gastric and Gastroesophageal Junction Adenocarcinomas to Direct Targeted Therapy: A Practical Approach

Mod Pathol. 2024 Nov;37(11):100589. doi: 10.1016/j.modpat.2024.100589. Epub 2024 Aug 2.

Abstract

Claudin-18.2 (CLDN18.2) expression evaluated by immunohistochemistry is a new biomarker for gastric and gastroesophageal junction adenocarcinomas that will soon have market authorization for implementation into routine clinical practice. Despite successful testing in the setting of clinical trials, no specific practical testing guidelines have been proposed. Several preanalytical and analytical variables may interfere with adequate CLDN18.2 staining interpretation; thus, this article provides practical guidance on CLDN18.2 testing and scoring in gastric and gastroesophageal junction adenocarcinomas to identify patients who may respond to targeted therapy with monoclonal antibodies directed against CLDN18.2. Based on available data, moderate to strong (2+/3+) membrane staining in ≥75% of adenocarcinoma cells is the proposed cutoff for clinical use of monoclonal antibody anti-CLDN18.2 (zolbetuximab).

Keywords: CLDN18.2; gastric cancer; immunohistochemistry; predictive biomarkers.

Publication types

  • Guideline
  • Review

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / metabolism
  • Adenocarcinoma* / pathology
  • Antibodies, Monoclonal / therapeutic use
  • Biomarkers, Tumor* / analysis
  • Claudins* / analysis
  • Claudins* / metabolism
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / pathology
  • Esophagogastric Junction* / pathology
  • Humans
  • Immunohistochemistry* / methods
  • Molecular Targeted Therapy
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Claudins
  • CLDN18 protein, human
  • zolbetuximab

Supplementary concepts

  • Adenocarcinoma Of Esophagus