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. 2025 Apr 30;16(2):671-678.
doi: 10.21037/jgo-2024-925. Epub 2025 Apr 27.

Claudin 18 immunohistochemistry in cholangiocarcinoma

Niyati Desai  1 , Huaibin M Ko  1 , Michael Lee  1 , Ladan Fazlollahi  1 , Ryan H Moy  2 , Sam S Yoon  3 , Helen Remotti  1 , Brynn Levy  1 , Andrew T Turk  1 , Stephen M Lagana  1
Affiliations

Claudin 18 immunohistochemistry in cholangiocarcinoma

Niyati Desai et al. J Gastrointest Oncol. .

Abstract

Background: Monoclonal antibodies against claudin (CLDN) 18.2 (a component of tight junctions) in gastric epithelial cells are an emerging therapeutic option for patients with advanced gastric and esophageal adenocarcinoma. Phase 2 and 3 trials have shown clinical efficacy in patients whose tumors show high expression of CLDN18 by immunohistochemistry, and the US Food and Drug Administration has recently approved a drug for patients with advanced gastric and gastroesophageal adenocarcinoma and high CLDN18 expression. Adenocarcinoma of the bile ducts, a.k.a. cholangiocarcinoma (CCA), may share morphologic and immunophenotypic qualities with gastric adenocarcinoma, and are lethal tumors with limited therapeutic options. The purpose of this study was to determine if primary tumors of the bile ducts show expression of CLDN18 with the use of a monoclonal antibody to CLDN18, and if so, if the extent of expression is similar to that seen in the gastric and esophageal tumors of patients who responded to anti-CLDN18.2 therapeutics.

Methods: Tissue microarrays containing 41 intrahepatic cholangiocarcinomas, 36 hilar cholangiocarcinomas, and 28 distal bile duct cholangiocarcinomas were stained with a monoclonal antibody which detects CLDN18 (Ventana 43-14A). The percentage of tumor cells staining and intensity was recorded for each case with tumors with 75% of cells showing moderate to strong intensity being considered high expressers.

Results: High expression was seen in 14.63% of intrahepatic, 8.3% of hilar, and 17.8% of distal bile duct cholangiocarcinomas. Overall, 13.33% of CCAs expressed CLDN18 to an extent which would qualify for treatment in the gastric and esophageal trials.

Conclusions: Given the poor prognosis and current lack of therapeutic options, trials of anti-CLDN18.2 inhibitors could be considered in patients with CCA and high expression of CLDN18 by immunohistochemistry.

Keywords: Claudin 18.2 (CLDN18.2); anti-CLDN18.2 monoclonal antibody; cholangiocarcinoma (CCA).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2024-925/coif). S.M.L. has received honoraria for serving as a panelist for Astellas Pharmaceuticals. R.M. has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from HMP Global for the lecture Great Debates & Updates in Gastrointestinal Malignancies and from MDOutlook for an educational event on immunotherapy in Upper GI cancers; received consulting fees from Puretech Health and has participated on a Data Safety Monitoring Board or Advisory Board of IDEAYA Biosciences and Nimbus Therapeutics; has received Drug Support from Verastem and Vivace Therapeutics and Research funding for institution from Repare Therapeutics and Nimbus Therapeutics. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Representative images of CLD18 expression in cholangiocarcinoma by immunohistochemistry. Representative low 1+ (A), moderate 2+ (B), and strong 3+ (C) expression of Ventana (43-14A) (200×).
See this image and copyright information in PMC

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