Claudin-18.2 expression is frequent in remnant gastric carcinoma and associated with microsatellite instability and Epstein-Barr viral infection phenotypes.

Claudin-18.2 (CLDN18.2)-targeted therapeutics have been rapidly evolving. CLDN18.2 expression has not been evaluated in remnant gastric carcinoma. In this study, we analysed clinicopathological and molecular characteristics, including CLDN18.2 expression between remnant and conventional gastric carcinoma. Immunohistochemistry for CLDN18.2, p53, HER2, ARID1A, E-cadherin, CDX2, and mismatch repair proteins, as well as Epstein-Barr virus in situ hybridisation (EBER), was conducted in 95 remnant gastric carcinomas and 314 conventional gastric carcinomas. Histological features were classified by Lauren classification and a morphomolecular classification. Patients with remnant gastric carcinoma were predominantly male, were older, and demonstrated less Helicobacter infection but more prevalent Epstein-Barr virus (EBV) infection than patients with conventional gastric carcinoma (p<0.001, p=0.004, p=0.009, and p<0.001, respectively). By morphomolecular classification, intestinal type was the least common histology in remnant gastric carcinoma, but the second most common histologic subtype in conventional gastric carcinoma (p=0.005). Remnant gastric carcinoma was highly associated with CLDN18.2 expression, but negatively associated with CDX2 expression when compared with conventional gastric carcinoma (p<0.001 and p=0.001, respectively). A binary logistic regression model showed that remnant gastric carcinoma, morphomolecular classification, Lauren classification, differentiation, loss of ARID1A expression, and EBV infection (p<0.001, p=0.002, p=0.005, p=0.001, p=0.02, and p=0.012, respectively) were independent factors in predicting positive CLDN18.2 expression. Remnant gastric carcinoma demonstrated distinct characteristics from conventional gastric carcinoma, with highly prevalent CLDN18.2 expression. Patients with remnant gastric carcinoma may benefit from CLDN18.2-targeting therapeutics.