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. 2025 Mar;28(2):264-274.
doi: 10.1007/s10120-024-01573-8. Epub 2024 Dec 11.

Expression of therapy target molecules in esophagogastric junction and Barrett's adenocarcinoma

Hiroyuki Abe #  1 , Masayuki Urabe #  2   3 , Koichi Yagi  2 , Hiroharu Yamashita  2   4 , Yasuyuki Seto  2   5 , Tetsuo Ushiku  6
Affiliations

Expression of therapy target molecules in esophagogastric junction and Barrett's adenocarcinoma

Hiroyuki Abe et al. Gastric Cancer. 2025 Mar.

Abstract

Background: Recently, novel molecular targeted therapies have been developed for gastric and esophageal adenocarcinomas. We examined the status of therapeutic target molecules in esophagogastric junction (EGJ) and Barrett's adenocarcinoma.

Methods: Tissue microarrays were constructed from 114 cases of non-Barrett's EGJ adenocarcinoma and 30 cases of Barrett's adenocarcinoma. Immunohistochemistry for mismatch repair proteins, PD-L1, HER2, CLDN18, FGFR2b, and EBER-ISH was performed. When HER2 immunohistochemistry was 2 + , gene amplification was examined using in situ hybridization.

Results: EBER positivity, mismatch repair deficiency, PD-L1 combined positive score (CPS) ≥ 1, CLDN18 expression ≥ 75%, FGFR2b expression, and HER2 positivity were observed in 7 (6.1%), 11 (9.6%), 70 (61.4%), 38 (33.3%), 6 (5.3%), and 11 (9.6%) cases of EGJ adenocarcinoma as well as in 0 (0%), 0 (0%), 23 (76.7%), 7 (23.3%), 2 (6.7%), and 6 (20.0%) cases of Barrett's adenocarcinoma, respectively. PD-L1 CPS ≥ 1 cases had longer recurrence-free survival (P = 0.001) and overall survival (P = 0.003) than CPS < 1 cases. Other target molecules were not associated with survival. A total of 93/114 (81.6%) cases of EGJ adenocarcinoma and 26/30 (86.7%) cases of Barrett's adenocarcinomas expressed at least one target molecule.

Conclusions: Most EGJ and Barrett's adenocarcinomas may be eligible for molecular targeted therapy. Appropriate patient stratification based on these molecular tests will be important for precision medicine of the EGJ and Barrett's adenocarcinoma.

Keywords: CLDN18; Esophago-gastric junction; FGFR2b; HER2; PD-L1.

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Conflict of interest statement

Declarations. Conflict of interest: FGFR2b antibody used in the study is provided by Daiichi-Sankyo Co., Ltd. All studies were performed by the authors, and Daiichi-Sankyo played no role in the study. There is no other conflict of interests.

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