Claudin 18.2 Expression and Outcomes of First-Line Chemoimmunotherapy in HER2-Negative Gastric or Gastroesophageal Junction Cancer: A Single-Center Retrospective Study

This study aimed to characterize claudin 18.2 (CLDN18.2) expression in HER2-negative gastric or gastroesophageal junction cancer (GC/GEJC) and to evaluate whether CLDN18.2 status is associated with clinicopathological features and outcomes after first line chemoimmunotherapy. We retrospectively analyzed 189 patients with HER2-negative GC/GEJC treated at our institution from October 2019 to September 2024. CLDN18.2 expression was assessed by immunohistochemistry using two prespecified positivity thresholds: moderate to strong membranous staining (2+) in ≥40% or ≥75% of tumor cells. CLDN18.2 positivity was observed in 92/189 patients (48.7%) using the ≥40% threshold and 69/189 (36.5%) using the ≥75% threshold. PD L1 CPS ≥ 5 was less frequent in CLDN18.2 positive than in CLDN18.2 negative tumors at both thresholds (≥40%: 8.7% vs. 23.7%, p = 0.003; ≥75%: 8.7% vs. 20.8%, p = 0.019). Among 87 patients receiving first line chemoimmunotherapy, CLDN18.2 status was not associated with significant differences in objective response rate, progression free survival, or overall survival. CLDN18.2 positive tumors showed lower PD L1 expression, but CLDN18.2 status did not identify a subgroup with differential benefit from first line chemoimmunotherapy. These findings suggest that CLDN18.2 status does not appear to serve as a predictive biomarker for immune checkpoint inhibitor-based treatment.