High fidelity of Claudin-18.2 expression in primary and matched metastatic (lymph nodes, peritoneum, and liver) pancreatic ductal adenocarcinoma: a foundation for targeted therapy

: Claudin-18.2 (CLDN18.2) is a tight-junction protein that can be expressed in various neoplasms, including pancreatic ductal adenocarcinoma (PDAC). Anti-CLDN18.2 targeted therapies have already been approved for CLDN18.2-positive gastric cancer and are currently being tested in clinical trials for PDAC. This study aims to define the expression patterns and concordance rate of CLDN18.2 in primary and matched metastatic PDAC. Whole-slide immunohistochemistry for CLDN18 was performed on primary PDAC and matched metastases, and was assessed by cell percentage (range: 0-100%) and intensity of CLDN18-positivity (scores 0, 1+, 2+, and 3+), and also using the H-score. Tumor positivity for CLDN18 was determined if ≥75% of tumor cells exhibited 2+/3+ staining. The study's cohort was composed of 20 patients with PDAC and concomitant lymph node metastases (LNM), 30 patients with PDAC and matched peritoneal metastases (PM), and 12 patients with PDAC and concomitant liver metastases (LIVM). The mean value of the percentages of 2+/3+ cells for primary tumors was 46.5%, for LNM was 60%, for PM was 31%, and for LIVM was 22%. The mean value of the H-score for primary tumors was 123.9, for LNM was 183, for PM was 89.1, and for LIVM was 54.6. The correspondence rate between primary PDAC and the matched metastatic sites was: 70.0% for PDAC/LNM, 93.3% for PDAC/PM, and 100.0% for PDAC/LIVM. This study shows a high rate of correspondence of CLDN18-positivity between primary PDAC and different metastatic sites, providing a strong rationale for further exploring and testing anti-CLDN18.2 therapeutic strategies in this lethal malignancy.