{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:38:33Z","timestamp":1788903513530,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T00:00:00Z","timestamp":1687651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare subset of alpha\u2010fetoprotein (AFP)\u2010producing carcinomas with poor prognosis. However, the molecular features associated with the malignant potential of GEAD remain partially elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>In this study, the relationship between clinicopathological parameters and aggressive biological behaviour was analysed in 37 patients with GAED. The results showed that GAED tended to infiltrate the deep layer of the gastric wall and possessed more frequent vascular invasion than conventional gastric adenocarcinoma (CGA) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). All distant metastases were observed in the GAED group, not the CGA group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). High HER2 expression was found in nearly 24.32% of the informative cases, and none showed EBV\u2010encoded RNA positivity or deficient mismatch repair. The most frequently mutated gene in GAED was <jats:italic>p53<\/jats:italic>. Programmed cell death\u2010ligand 1 (PD\u2010L1) immunostaining revealed 13 patients with a combined positive score (CPS)\u2009\u2265\u20095 (65%, 13 of 20). Thus, based on these molecular markers (immunostaining, <jats:italic>in situ<\/jats:italic> hybridisation and mutation analysis), GAED may be classified as a unique subgroup of the chromosomal instability subtype with HER2<jats:sup>+<\/jats:sup>\/EBV<jats:sup>\u2212<\/jats:sup>\/MSS\/TP53<jats:sup>+<\/jats:sup>\/PD\u2010L1<jats:sup>+<\/jats:sup>. Next\u2010generation sequencing analyses showed that mutations in the <jats:italic>TOPI<\/jats:italic>, <jats:italic>ELOA<\/jats:italic> and <jats:italic>NOTCH3<\/jats:italic> genes were found only in GAED, and abnormally expressed genes in GAED were significantly enriched in hepatocellular carcinoma\u2010, gland development\u2010, and gastric cancer\u2010related pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The HER2<jats:sup>+<\/jats:sup>\/EBV<jats:sup>\u2212<\/jats:sup>\/MSS\/TP53<jats:sup>+<\/jats:sup>\/PD\u2010L1<jats:sup>+<\/jats:sup> profile and hepatocellular carcinoma\u2010related pathways may be significant in the malignant potential of GAED. In addition to anti\u2010HER2 therapy, immune check\u2010point inhibitors may be an effective treatment option for patients with GAED.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14998","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T01:09:15Z","timestamp":1687741755000},"page":"631-646","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Exploring the molecular characteristics of the malignant potential of gastric adenocarcinoma with enteroblastic differentiation"],"prefix":"10.1111","volume":"83","author":[{"given":"Yong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital  Tianjin 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