P-217 A retrospective, pathologist-based assessment of immunohistochemistry assay for CLDN18.2 expression in digestive system adenocarcinoma

Claudin 18 (CLDN18) represents an attractive drug target for gastric and pancreatic cancers. A more comprehensive understanding of CLDN18 expression is essential for future implanting of effective digestive system adenocarcinomas (DSAs) management. We conducted a retrospective immunohistochemistry evaluation of CLDN18 expression in five DSAs (n = 834) using the anti-CLDN18 (clone 43-14A) antibody. Cases with immunochemistry staining signaling 2+–3+ intensity in ≥75% of tumor cells were defined as positive. We observed higher positive rates (cut-off ≥75%) of CLDN18 in three DSAs: gastric adenocarcinomas (GAD, 46.1%), pancreatic adenocarcinomas (PAAD, 26.0%), and gallbladder adenocarcinomas (GBAD, 12.4%); whereas CLDN18-positive cases were rarely identified in colorectal adenocarcinomas (COAD, 1.7%) and intrahepatic cholangiocarcinoma (IHCC, 10.1%). In PAAD, a high CLDN18-positive rate was determined in patients with well differentiation, no peripheral fat invasion, and at the early pTNM stage. In GBAD, the higher positive rate was in the subgroups with younger age (< 60 years old), well differentiation, or at the early pT stage, pN stage, or pTNM stage. CLDN18-positive GBAD patients showed significantly better overall survival (OS) and disease-free survival (DFS) than the patients with low CLDN18 expression. Three types of DSAs with high levels of CLDN18 expression, GAD, GBAD, and PAAD, may benefit most from future anti-CLDN18 therapies. The correlations of the expression of CLDN18 with clinicopathological characteristics and prognosis suggest that the patients at an early stage could benefit more from the future anti-CLDN18 treatment and CLDN18 can function as a pivotal regulative molecule in GBAD.