Claudin 18.2: a promising actionable target in biliary tract cancers

Area of Science:

• Oncology
• Gastroenterology
• Molecular Pathology

Background:

• Anti-claudin 18.2 (anti-CLDN18.2) therapy is approved for CLDN18-positive gastric and gastroesophageal junction adenocarcinomas.
• The expression of CLDN18 in biliary tract cancers (BTCs) is not well-characterized.

Purpose of the Study:

• To evaluate the expression of CLDN18 in a large cohort of pathologically characterized BTCs.
• To determine the potential of CLDN18 as a therapeutic target in BTCs.

Main Methods:

• A total of 237 BTC samples were collected and analyzed for CLDN18 status using immunohistochemistry.
• CLDN18 positivity was defined as ≥75% of tumor cells with moderate-to-strong membranous staining.

Main Results:

• CLDN18 expression was observed in 29.5% of BTCs.
• Gallbladder carcinoma (GBC) and extrahepatic cholangiocarcinoma (eCCA) showed significantly higher CLDN18 expression rates (62.5% and 53.4%, respectively) compared to intrahepatic cholangiocarcinoma (iCCA; 12.9%).
• CLDN18 positivity was found in 5.5% of BTCs, with higher rates in GBC (15.6%) and eCCA (8.6%) than in iCCA (2.0%). In iCCAs, the large duct subtype exhibited higher CLDN18 expression and positivity than the small duct subtype.

Conclusions:

• CLDN18 is expressed in a subset of BTCs, with notable prevalence in GBC and eCCA.
• CLDN18 expression in iCCA is more frequent in the large duct subtype and not associated with IDH1 or FGFR2 status.
• CLDN18 represents a potential therapeutic target for BTCs, meriting further clinical investigation.