Expression of Claudin18.2 in metastatic lesions in peritoneum of gastric cancer.

Background: Patients with advanced gastric cancer (GC) with peritoneal involvement have a dismal prognosis. Recent clinical trials have shown that anti-Claudin18.2 (CLDN18.2) antibody (zolbetuximab) enhances survival in patients with GC expressing high levels of CLDN18.2. However, the effectiveness of the zolbetuximab in patients with peritoneal metastases (PMs) remains unclear. In this study, we aimed to evaluate the expression of CLDN18.2 in disseminated lesions to assess the clinical utility of zolbetuximab in the treatment of GC with PM. Methods: In 42 patients diagnosed with stage IV GC with PM, biopsy samples from the primary tumors and peritoneal metastatic nodules were collected and immunostained using the specific antibody (43-14A, Ventana). The expression of CLDN18.2 was comparatively evaluated based on staining intensity and the proportion of positive cells. Results: Positive immunoreactivity of CLDN18.2 was observed in 37 (88%) of the primary tumors. Specifically, CLDN18.2 positivity was identified in 26 (62%) or 12 (29%) patients based on moderate to strong membrane staining in at least 40% or 75% of tumor cells, respectively. In comparison, the staining intensity in tumor cells was consistently reduced in PM across all patients. CLDN18.2 expression was absent in PM of 29 (69%) patients, while 3 (7.1%) cases were determined to be CLDN18.2-positive based on a cutoff value of 40% for high staining. This trend was particularly pronounced in cases with undifferentiated type and human epidermal growth factor receptor 2 (HER-2) negative primary tumors. Conclusions: Although CLDN18.2 expression in PM mirrored that in primary lesions, the levels were generally reduced. When zolbetuximab is used for GC patients with peritoneal involvement, it is preferable to assess the expression of CLDN18.2 in the disseminated lesions.