Abe Hiroyuki, Urabe Masayuki, Yagi Koichi, Yamashita Hiroharu, Seto Yasuyuki, Ushiku Tetsuo
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Gastric Cancer. 2025 Mar;28(2):264-274. doi: 10.1007/s10120-024-01573-8. Epub 2024 Dec 11.
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.
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.
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.
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.
最近，已开发出针对胃和食管腺癌的新型分子靶向疗法。我们研究了食管胃交界（EGJ）和巴雷特腺癌中治疗靶点分子的状态。
从114例非巴雷特EGJ腺癌和30例巴雷特腺癌构建组织微阵列。进行错配修复蛋白、PD-L1、HER2、CLDN18、FGFR2b的免疫组织化学检测以及EBER原位杂交检测。当HER2免疫组织化学结果为2+时，使用原位杂交检测基因扩增情况。
在EGJ腺癌病例中，EBER阳性、错配修复缺陷、PD-L1联合阳性评分（CPS）≥1、CLDN18表达≥75%、FGFR2b表达以及HER2阳性的病例分别有7例（6.1%）、11例（9.6%）、70例（61.4%）、38例（33.3%）、6例（5.3%）和11例（9.6%）；在巴雷特腺癌病例中，上述情况分别为0例（0%）、0例（0%）、23例（76.7%）、7例（23.3%）、2例（6.7%）和6例（20.0%）。PD-L1 CPS≥1的病例比CPS<1的病例无复发生存期更长（P = 0.001），总生存期也更长（P = 0.003）。其他靶点分子与生存情况无关。总共93/114例（81.6%）EGJ腺癌病例和26/30例（86.7%）巴雷特腺癌病例表达至少一种靶点分子。
大多数EGJ和巴雷特腺癌可能适合分子靶向治疗。基于这些分子检测进行适当的患者分层对于EGJ和巴雷特腺癌的精准医疗很重要。
