Claudin 18.2 expression in esophageal adenocarcinoma and its potential impact on future treatment strategies

The incidence of esophageal adenocarcinoma (EAC) has rapidly increased, particularly in the Western world. Despite improvements in perioperative treatments, the overall survival of patients remains low. Claudin 18.2 is a tight junction protein that is exclusively expressed in the gastric epithelia. However, following malignant transformation, gastric cancer metastases maintain this expression. Therefore, claudin 18.2 is a promising target for immunotherapy. Previous clinical trials have revealed improved anti-tumor activity in patients treated with an anti-claudin antibody by investigating the expression of claudin 18.2 in tumor cells. However, there is currently very limited data on the importance of claudin 18.2 expression in EAC. The present study analyzed the distribution of claudin 18.2 using immunohistochemistry in 485 patients with EAC, including their lymph node metastases. Additionally, these results were associated with clinical and molecular data. Claudin 18.2 was detected in 89/485 patients (18.4%). No correlations between expression and clinicopathological data (sex, age, pT stage, lymph node metastasis and grading) were observed. However, significantly decreased claudin 18.2 expression was observed in tumor types with upregulated human epidermal growth factor receptor 2 expression (P=0.036). Additionally, neoadjuvant treatment did not have any significant impact on claudin 18.2 expression (P=0.331). To the best of our knowledge, the present study is the largest systematic investigation of claudin 18.2 protein expression in EAC. The results obtained suggested that claudin 18.2 may serve as a promising therapeutic target in a substantial number of patients with EAC.