Claudin 18.2 Expression Concordance in Paired Cytology and Surgical Specimens of Gastric and Gastroesophageal Junction Adenocarcinomas

Context.—: Claudin 18.2 (CLDN18.2) is a clinically actionable target in gastric and gastroesophageal junction adenocarcinomas, with patient selection guided by CLDN18.2 immunohistochemistry assay. While surgical specimens are standard for testing, the reliability of cytology specimens for CLDN18.2 assessment remains unclear. Objective.—: To assess the concordance of CLDN18.2 expression between cytology and surgical specimens and to explore the possible causes of discrepancy. Design.—: CLDN18.2 immunohistochemistry was performed on paired cytology and surgical specimens. The diagnostic performance at the cutoff of 75% or greater was evaluated across clinicopathologic variables. Results.—: Positive CLDN18.2 expression was seen in 35% (13 of 37) of surgical and 32% (12 of 37) of cytology cases. Overall, 86% (32 of 37) of pairs were concordant (either positive or negative). At the cutoff of 75% or greater, cytology achieved 77% sensitivity, 92% specificity, 83% positive predictive value, and 88% negative predictive value. Subgroup analysis showed that specimen origin was the strongest determinant of accuracy: concordance was greatest when both cytology and surgical specimens were obtained from gastric primary tumor, with perfect agreement (prevalence-adjusted, bias-adjusted κ [PABAK] = 1.00). In contrast, cases where one or both specimens were derived from metastatic sites showed lower agreement (PABAK = 0.68; bootstrap P < .01). Conclusions.—: Cytology specimens could serve as a reliable source for CLDN18.2 biomarker testing when interpreted at the threshold of 75% or above. Although discrepancies occur in some cases, the findings support the incorporation of cytology into biomarker testing workflows to expand access to CLDN18.2-targeted therapies for patients lacking surgical specimens.