Evaluation of Claudin 18.2 Expression Changes Following Chemotherapy in Pancreatic Ductal Adenocarcinoma

BACKGROUND/AIM: Although Claudin 18.2 (CLDN18.2) is a promising therapeutic target in pancreatic ductal adenocarcinoma (PDAC), its longitudinal expression dynamics after chemotherapy remain unclear. In this study, we aimed to evaluate CLDN18.2 expression changes in paired pre- and post-chemotherapy specimens and to examine its clinicopathological and prognostic significance. PATIENTS AND METHODS: We retrospectively analyzed 74 patients with PDAC who underwent pancreatectomy after preoperative chemotherapy at Kumamoto University Hospital between 2017 and 2024. CLDN18.2 protein expression was evaluated using immunohistochemistry assays in fine-needle aspiration biopsy (FNAB) samples obtained prior to chemotherapy and in corresponding resected specimens. The associations between CLDN18.2 expression levels and clinicopathological features were analyzed, along with longitudinal changes in CLDN18.2 expression. RESULTS: CLDN18.2 positivity was observed in 31 (41.9%) pre-treatment specimens and 18 (24.3%) post-treatment specimens. CLDN18.2 expression was not associated with any clinicopathological factor in the pre-treatment specimens. However, in the post-treatment specimens, CLDN18.2 positivity was significantly associated with well-differentiated tumors and lower pre-chemotherapy CA19-9 levels compared with CLDN18.2-negative cases. Neither overall survival nor recurrence-free survival differed significantly between the CLDN18.2-positive and CLDN18.2-negative groups. Paired analysis demonstrated that CLDN18.2 expression levels were significantly decreased in post-treatment specimens compared with pre-treatment specimens. CONCLUSION: In our PDAC patient cohort, CLDN18.2 expression levels were significantly reduced following preoperative chemotherapy. These findings suggest that chemotherapy may alter CLDN18.2 expression patterns and may have implications for reassessing the CLDN18.2 status after treatment when considering future CLDN18.2 targeted therapy.