Clinicopathological significance of histological diversity in gastric adenocarcinoma with primitive enterocyte phenotype: A methylation-driven aggressive entity

doi:10.3748/wjg.v31.i28.108990

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World Journal of Gastroenterology

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Basic Study

World J Gastroenterol. Jul 28, 2025; 31(28): 108990
Published online Jul 28, 2025. doi: 10.3748/wjg.v31.i28.108990

Clinicopathological significance of histological diversity in gastric adenocarcinoma with primitive enterocyte phenotype: A methylation-driven aggressive entity

Hou-Qiang Li, Lan-Qing Zheng, Wen-Tao Huang, Xun-Bin Yu, Xia Zhang, Lan Lin, Shan-Shan Lv, Xi-Yao Yan, Xiao-Yan Chen

Hou-Qiang Li, Xun-Bin Yu, Xia Zhang, Lan Lin, Shan-Shan Lv, Xi-Yao Yan, Xiao-Yan Chen, Department of Pathology, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, Fujian Province, China

Hou-Qiang Li, Department of Pathology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, Fujian Province, China

Hou-Qiang Li, Department of Pathology, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China

Lan-Qing Zheng, Department of Nursing, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, Fujian Province, China

Wen-Tao Huang, Department of Hepato-Pancreato-Biliary Surgery, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350005, Fujian Province, China

Author contributions: Li HQ conceptualized, wrote and reviewed the paper, and designed the experiments; Li HQ, Zheng LQ, Zhang X, Yu XB, Lin L, Yan XY, and Lv SS performed the experiments; Li HQ and Zheng LQ analyzed the data; Li HQ, Zheng LQ, Yu XB, Huang WT, and Chen XY provided reagents/materials/analysis tools; and all authors have read and approved the final manuscript.

Supported by the Startup Fund for Scientific Research, Fujian Medical University, No. 2020QH1168; Fujian Provincial Science and Technology Innovation Joint Funds, No. 2024Y9023; and the Fujian Provincial Natural Science Foundation of China, No. 2024J011644.

Institutional review board statement: This study was approved by the Medical Ethics Committee of Fujian Provincial Hospital, approved No. K2021-04-094.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: The data presented in this study are available upon request from the corresponding author on reasonable request.

Corresponding author: Hou-Qiang Li, Researcher, Department of Pathology, Fuzhou University Affiliated Provincial Hospital, No. 134 East Street, Fuzhou 350001, Fujian Province, China. docli254@163.com

Received: April 28, 2025
Revised: May 22, 2025
Accepted: June 23, 2025
Published online: July 28, 2025
Processing time: 87 Days and 23 Hours

Core Tip

Core Tip: Gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) exhibits aggressive behavior and diverse morphologies, including tubular-papillary and solid types, which necessitate integrated histopathological, immunohistochemical, and molecular experiments for accurate identification. This study highlighted GAPEP’s methylation-driven pathogenesis, with methylation dysregulation (e.g., DNMT3A/B/L, TET1/3 and EZH2 upregulation). Gastric adenocarcinoma with enteroblastic differentiation and hepatoid adenocarcinoma shared similar clinicopathological and genetic features, suggesting a common origin. Targeting methylation pathways (e.g., DNMT inhibitors) offers potential therapeutic avenues for this lethal cancer, emphasizing the critical role of epigenetic mechanisms in the pathogenesis of GAPEP.