Expression profiles of cadherin 17 and claudin 18.2 in comparison with peptide hormonal expression in pancreatic neuroendocrine tumours: Implications for targeted immunotherapy

Abstract

Cadherin 17 (CDH17) and claudin 18.2 (CLDN18.2) are highly selective markers of intestinal and gastric lineages and are expressed in adenocarcinomas of various organs. They have also been identified as potential targets for immunotherapy. Expression of CDH17 and CLDN18.2 has been observed in a subset of pancreatic neuroendocrine tumours (PanNETs). This study investigates the immunohistochemical expression of CDH17 and CLDN18 in PanNETs in comparison with hormonal expression profiles to provide baseline data for determining candidate indications for targeted therapy with CDH17 and CLDN18.2 in PanNETs, including insulinomas (n = 22), glucagonomas (n = 13), gastrinomas (n = 3), serotoninomas (n = 2) and PanNETs not otherwise specified (NOS) (n = 17). In the normal pancreas, CDH17 was expressed in the lateral membrane of ducts and some islet cells, whereas CLDN18 was occasionally expressed in the intercalated ducts and centroacinar cells. In PanNETs, CDH17 and CLDN18 was detected by membranous staining. CDH17 expression was observed in 10 of 17 (58.8 %) PanNETs NOS, 3 of 13 (23.1 %) glucagonomas, 1 of 3 (33.3 %,) gastrinomas, 1 of 2 (50 %) serotoninomas, and none of the insulinomas. According to predefined criteria, 7 of 17 (41.2 %) PanNETs NOS, 1 of 3 (33.3 %) gastrinomas, and 1 of 2 (50 %) serotoninomas were classified as CDH17-positive. There were no significant differences in clinicopathological features between CDH17-positive and CDH17-negative PanNETs, except for a higher tumour grade in the former (p<0.05). For CLDN18, expression was noted in 2 out of 3 (66.7 %) gastrinomas, one with focal staining and the other with diffuse staining. One of three (33.3 %) gastrinomas was classified as CLDN18-positive using predefined criteria. These findings suggest that a particular subset of PanNETs, including PanNET NOS, gastrinoma, and serotoninoma, may be potential candidates for CDH17-targeted immunotherapy. Additionally, gastrinoma may be a potential candidate for immunotherapy targeting CLDN18.2.