Temporal and spatial expression of CLDN18.2 in gastric cancer and gastroesophageal junction cancer.

Abstract

4054 Background: Recent studies have demonstrated the promising efficacy of CLDN18.2-targeted therapy in patients with gastric cancer (GC) or gastroesophageal junction cancer (GEJC) who are positive for CLDN18.2. This study aims to investigate the temporal and spatial consistency of CLDN18.2 expression in GC and to provide a comprehensive overview of its expression patterns. Methods: The expression of CLDN18.2 in primary GC tumors (biopsy/surgical) and corresponding peritoneal metastases (PM) was evaluated by quantifying cell membrane staining intensity with a validated semi-quantitative assay. CLDN18.2 positivity was defined when tumor cells with staining intensity (2+) and (3+) summed up to ≥ 75% of all. The Kappa test evaluated CLDN18.2 expression consistency across sample types, and the McNemar test compared its positive rates in paired samples. Results: Between February 2023 and April 2024, 536 patients were enrolled at the Gastric Cancer Center of West China Hospital, Sichuan University. The cohort comprised 399 in-situ biopsy samples, 240 radical gastrectomy samples, and 27 peritoneal biopsy samples. Among them, 109 patients had biopsy and surgical specimens, and 26 underwent preoperative neoadjuvant therapy. Among 399 biopsy specimens, 131 (32.8%) had positive CLDN18.2. In 240 surgical specimens, 167 (27.9%) were positive. In 27 peritoneal nodule specimens, 10 (37.0%) were positive. No significant differences were found (χ 2 = 2.128, P = 0.345). Among 109 patients with paired biopsy and postoperative pathology, CLDN18.2 expression concordance was 80.7% (88/109, Kappa = 0.562). In 27 peritoneal metastasis patients, it was 77.8% (21/27, Kappa = 0.503). For 26 chemo-resected patients, the pre-and post-chemo positive concordance was 80.8% (21/26, Kappa = 0.524). All showed moderate consistency. CLDN18.2 expression significantly correlated with several factors, including gender ( P = 0.002), histological subtype ( P = 0.003), tumor location ( P = 0.007), histological classification ( P = 0.035), and EBV status ( P = 0.006). Higher rates were in females, signet-ring cell carcinoma, non-GEJ tumors, poorly differentiated tumors, and EBV-positive patients. Conclusions: CLDN18.2 is widely present in both primary gastric cancer and peritoneal metastatic lesions. Expression consistency exists moderately between biopsy and surgical specimens, and primary and metastatic tissues. Consistency stays strong pre- and post-neoadjuvant therapy. Its expression links to clinical and molecular traits. This study comprehensively analyzed it, providing a better basis for CLDN18.2-targeted patient selection.