High Claudin 18.2 Expression Predicts Favorable Outcomes in Pancreatic Ductal Adenocarcinoma After Curative Resection

Background/Aim:

Pancreatic ductal adenocarcinoma (PDAC) exhibits aggressive clinical behavior and poor prognosis, primarily due to late-stage diagnosis, early metastasis, and treatment resistance. Current therapeutic approaches, including operation, chemotherapy, and radiotherapy, demonstrate limited efficacy, underscoring the urgent need for novel targeted approaches. Claudin 18.2 (CLDN18.2) has emerged as a promising monoclonal antibody target, such as zolbetuximab; however, limited studies have examined its role in PDAC. This study investigated the association between CLDN18.2 expression and patient outcomes to inform potential therapeutic strategies.

Materials and Methods:

CLDN18.2 expression was evaluated by immunohistochemistry (IHC) on tissue microarrays from 95 patients with PDAC and quantified using the H-score method. Samples were categorized into high-expression (H-score ≥200) and low-expression (H-score <200) groups.

Results:

High CLDN18.2 expression was identified in 20 (21.1%) of 95 cases and was significantly associated with better tumor differentiation (p=0.016), absence of lymphatic invasion (p<0.001), lower lymph node ratio (p=0.028), and lower N stage (p=0.002). Survival analyses revealed that patients with high CLDN18.2 expression had prolonged overall survival (p=0.026, log-rank test) and recurrence-free survival (p=0.009, log-rank test) compared to those with low expression. Among patients receiving curative resection with adjuvant chemotherapy, high CLDN18.2 expression correlated with improved recurrence-free survival (p=0.010).

Conclusion:

High CLDN18.2 expression is associated with favorable clinicopathologic characteristics and improved survival outcomes in PDAC, especially among patients receiving adjuvant chemotherapy, suggesting its potential as a therapeutic and prognostic marker.