Prognostic Value of Intratumoral Expression of Claudin 18.2 in Resected Pancreatic Cancer.

BACKGROUND

Targeting Claudin-18 isoform 2 (CLDN18.2) improves survival in CLDN18.2 positive advanced gastric cancer and similar trials on metastatic pancreatic ductal adenocarcinoma (PDAC) are ongoing. Here, we aimed to assess the prevalence of CLDN18.2 positivity in resected PDAC including its association with overall survival (OS).

METHODS

Immunohistochemical analysis on paraffin-embedded primary tumors and lymph node metastases was performed from patients who underwent curative-intent PDAC resection at four centers in Sweden and Finland. In addition, survival outcomes were assessed.

RESULTS

In total, 599 primary tumors and 197 lymph nodes were analyzed. CLDN18.2 positivity was observed in 138 of 599 of primary tumors (23%) and 35 of 197 metastatic lymph nodes (17.8%). CLDN18.2 positivity in primary tumors was associated with higher tumor grade (p = 0.016). Median OS was longer in patients with CLDN18.2-positive tumors (27.7 vs. 21.1 months). Adjusted analysis identified CLDN18.2 positivity as an independent prognostic variable for OS (hazard ratio 0.79; 95% confidence interval 0.64-0.98).

CONCLUSIONS

CLDN18.2 is expressed in 23% of primary PDAC tumours, indicating its potential to be used as a therapeutic target in a significant proportion of PDAC patients, and its expression is associated with improved OS in resected PDAC, supporting its role as a prognostic marker.