Identifying the Claudin 18.2-Positive Gastric Cancer Population for Targeted Therapy

Overview

Claudin 18.2 is a tight-junction protein normally found in healthy gastric mucosa, but in a meaningful subset of tumors it stays expressed on the cancer cell surface where a therapy can reach it. Immunohistochemistry, or IHC, is the standard method used to detect this protein on a tumor sample. The goal of testing is to separate patients whose gastric or gastro-esophageal junction cancer expresses Claudin 18.2 from those who do not, so treatment can be matched to the tumor's biology.

How IHC Defines the Target Population

A pathologist stains a biopsy section and scores how many tumor cells show moderate-to-strong membrane staining. Trials of the anti-Claudin 18.2 antibody zolbetuximab used a cutoff around 75 percent of tumor cells with moderate-to-strong expression to select patients. Roughly 30 to 40 percent of gastric adenocarcinomas fall into this positive group, which means testing is essential before assuming a patient qualifies for Claudin 18.2-directed therapy.

Why Biomarker Selection Matters Clinically

Targeted antibodies work only when the antigen is actually present, so treating an unselected population dilutes benefit and exposes patients to side effects without reason. A clear positive IHC result tells the care team that the tumor displays the surface target the drug is designed to bind through immune mechanisms. For payers and hospitals, documented biomarker status also supports appropriate use of a specialized biologic.

Ordering and Interpreting the Test

Labs report the staining percentage and intensity alongside the cutoff used, because different assays can vary. A fresh or archived tumor sample is usually sufficient, and the result should be reviewed by a qualified pathologist. Clinics building a gastrointestinal program should confirm that their pathology partner uses a validated Claudin 18.2 assay with a defined positive threshold.

FAQ

Q: What is Claudin 18.2 in gastric cancer? A: It is a tight-junction protein that remains on the surface of some gastric and gastro-esophageal junction tumor cells, making it a target for anti-Claudin 18.2 antibodies such as zolbetuximab.

Q: How is a patient found to be positive? A: Through immunohistochemistry on a tumor biopsy, scored by the percentage of cells with moderate-to-strong membrane staining, often using a threshold near 75 percent of tumor cells.

Q: What fraction of gastric cancers express Claudin 18.2? A: Approximately 30 to 40 percent of gastric adenocarcinomas show the expression pattern used to select patients, which is why routine biomarker testing is recommended before treatment.