Claudin 18 immunohistochemistry in cholangiocarcinoma

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.

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.

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.

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.