Prevalence and prognostic value of Claudin 18.2 expression in pancreatic ductal adenocarcinoma.

Abstract

4188 Background: Although Claudin18.2 expression (CLDN18.2) has been investigated in pancreatic ductal adenocarcinoma (PDAC), prevalence and prognostic significance remain inconsistent. This study evaluated both the prevalence and prognostic value of CLDN18.2 expression in PDAC. Methods: CLDN18.2 expression was assessed by IHC on FFPE tumor samples from 201 patients with PDAC enrolled in the BIOPAC study (NCT03311776) between Jan 2013-Feb 2024. Staining was performed using the Ventana CLDN18 (43) CE IVD Assay (Roche Diagnostic Solutions). All slides were independently scored by two pathologists, with discrepancies resolved by consensus. Positive expression was defined as moderate (+2) or strong (+3) staining in ≥75% of tumor cells. Patients with non-metastatic disease were excluded from the survival analysis to reduce prognostic confounding. OS and PFS were evaluated using Kaplan-Meier estimates, log-rank tests, and multivariable Cox models adjusted for stage, age, sex, chemotherapy type, diabetes, ECOG performance status, Body Mass Index, and Charlson Age-Adjusted Comorbidity Index. Associations with clinicopathological variables were evaluated using Mann-Whitney U, χ², or Fisher’s exact tests with Bonferroni correction (p < 0.05 considered significant). Results: Of 201 patients, 56 had non-metastatic disease and 145 had metastatic disease. Positive CLDN18.2 expression was detected in 54 tumors (27% overall): 14 (25%) non-metastatic and 40 (28%) in metastatic cases. In patients with metastatic disease, the median OS was 9.9 months (95% CI, 6.7-12.8) in the CLDN18.2 positive group and 6.3 months (95% CI, 4.9-8.5) in the negative group, with a significant difference as demonstrated by log-rank test (p = 0.009). CLDN18.2 positivity was associated with improved OS in univariate analysis (HR = 0.60; 95% CI 0.41-0.89; p = 0.010) but was not statistically significant after adjustment for covariates (HR = 0.69; 95% CI 0.47-1.02; p = 0.064). A similar pattern was observed for PFS, with median PFS of 6.0 months (95% CI, 3.6-7.6) in the CLDN18.2 positive group and 4.1 months (95% CI, 3.4-5.3) in the negative group (log-rank p = 0.036). The unadjusted association between CLDN18.2 positivity and longer PFS (HR = 0.67; 95% CI 0.46-0.98; p = 0.037), was not maintained after multivariable adjustment (HR = 0.67; 95% CI 0.43-1.03; p = 0.066). No significant associations were identified between CLDN 18.2 expression and clinicopathological variables after correction for multiple testing. Conclusions: CLDN18.2 was expressed in 27% of PDAC tumors. While its association with OS and PFS was not statistically significant after adjustment for clinical covariates, its prevalence in metastatic cases highlights its potential relevance as a therapeutic target in PDAC. Ongoing validation in an expanded cohort may further clarify the prognostic and predictive significance of CLDN18.2 expression.