Claudin18.2 expression and clinicopathological features in cytology effusion specimens from gastric adenocarcinoma: A comparative study with tissue specimens

Background Zolbetuximab (IMAB362) is under investigation for treating advanced gastrointestinal tumors because it targets Claudin18.2 (CLDN18.2). CLDN18.2 is a promising molecule along with the presence of human epidermal growth factor receptor 2 in gastric cancer. This study evaluated cell block (CB) preparations of serous cavity effusions for the feasibility for CLDN18.2 protein expression and compared the results with those of biopsy or resection specimens. The association of CLDN18.2 expression in effusion samples and the clinicopathological features were also investigated. Methods Cytological effusion specimens and matched surgical pathology biopsy or resection specimens of 43 gastric and gastroesophageal junctional cancer cases were stained for CLDN18.2 expression and quantified using immunohistochemistry based on the manufacturer's instructions. Results Positive staining was detected in 34 (79.1%) tissue and 27 (62.8%) effusion CB samples in this study. When “positivity” was defined as moderate‐to‐strong staining in ≥40% viable tumor cells, CLDN18.2 expression was observed in 24 (55.8%) tissue and 22 (51.2%) effusion CB samples. A cutoff of 40% for CLDN18.2 positivity was used to demonstrate high concordance (83.7%) between cytology CB and tissue specimens. The results showed that CLDN18.2 expression in effusion specimens correlated with tumor size (p = .021) but not with sex, age at diagnosis, primary tumor location, staging, Lauren phenotype, cytomorphologic features, or Epstein‐Barr virus infection. Cytological effusions with or without CLDN18.2 expression did not significantly affect overall survival. Conclusions This study's results show that serous body cavity effusions may be suitable for CLDN18.2 biomarker testing; however, discordant cases should be interpreted cautiously. This study aimed to assess the feasibility of using cell blocks prepared from a serous cavity effusion sample along with biopsy and resection specimens from relevant surgical pathology to confirm Claudin18.2 expression by immunohistochemistry. The results demonstrated that there was high concordance (83.7%) of Claudin18.2 immunoperoxidase results between cytology effusion cell block and tissue specimens when a cutoff of 40% was used for Claudin18.2 positivity.