Retrospective analysis of Claudin 18.2 expression in 64 patients with advanced gastrointestinal peritoneal disease: a potential therapeutic target for high-grade appendiceal mucinous carcinoma.

AIMS: Specific to normal gastric epithelium, Claudin 18.2 (CLDN18.2) is a tight junction protein. CLDN18.2 immunohistochemistry is a companion diagnostic used to identify oesophageal and gastric adenocarcinoma patients eligible for targeted therapy with zolbetuximab. It has demonstrated survival benefits in advanced upper gastrointestinal (UGI) cancers, with many studies now exploring its potential use beyond the UGI tract. This study aimed to examine CLDN18.2 expression in a peritoneal malignancy patient cohort. METHODS: CLDN18.2 immunohistochemistry was performed on archived tissue from patients who underwent cytoreductive surgery at a national centre for peritoneal malignancy. CLDN18.2 immunoprofiles were compared in two key tumour cohorts: peritoneal metastases from colorectal adenocarcinoma and appendiceal mucinous neoplasms. Positivity was defined as moderate-to-strong membranous staining in >75% of tumour cells. In addition, any CLDN18.2 positivity in tumour cells (>0% of cells showing moderate-to-strong membranous staining) was recorded in all cases. RESULTS: 64 cases were examined; primary tumour sites of origin were colorectal (n=34, 53%) and appendiceal (n=30, 47%). CLDN18.2 positivity in the overall appendiceal group was 17% compared with 3% in colorectal adenocarcinomas (p=0.090). In the appendiceal group, CLDN18.2 positivity was only demonstrated in high-grade appendiceal mucinous carcinomas (22%, 5 of 23). CLDN18.2 positive staining (>0% of tumour cells) was significantly increased in the appendiceal group compared with colorectal adenocarcinoma (53% vs 3%, respectively) (p<0.0001). CONCLUSIONS: These results demonstrate CLDN18.2 expression in a subset of appendiceal peritoneal metastases. This is one of the first focused studies showing CLDN18.2 expression in this tumour group, perhaps highlighting a future role for targeted therapies in those with limited curative oncological options.