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Purpose: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs).
Materials And Methods: Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed.
Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS.
Conclusion: We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016830 | PMC |
http://dx.doi.org/10.4143/crt.2024.667 | DOI Listing |
Endocr Pathol
August 2025
Institute of Pathology, Philipps University Marburg und University Hospital Marburg, Marburg, Germany.
Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNEN) are usually highly aggressive tumors characterized by marked histological heterogeneity, most commonly represented by mixed adenocarcinoma and poorly differentiated neuroendocrine carcinoma (NEC). However, beyond morphological observations, the biological basis and implications of this heterogeneity remain incompletely understood. In this study, we combined component-specific next-generation sequencing and spatial transcriptomics to investigate three mixed adenocarcinoma-NEC cases from different anatomical sites (ileocecal, ovarian, gastric), tracing tumor progression from precursor lesions to invasive NEC.
View Article and Find Full Text PDFCancers (Basel)
July 2025
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
Purpose: Neuroendocrine carcinomas (NECs) are aggressive tumors treated with cisplatin-based chemotherapy, though responses vary. As DNA damage response (DDR) pathways influence cisplatin sensitivity, this single-center retrospective study evaluates the efficacy of first-line cisplatin in recurrent or metastatic NEC based on DDR mutation status.
Materials And Methods: This study analyzed patients with grade 3 recurrent or metastatic NEC treated with first-line etoposide plus cisplatin at Samsung Medical Center between January 2019 and September 2023.
PLoS One
August 2025
Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Institute of Science Tokyo, Tokyo, Japan.
Introduction: Comprehensive genomic profiling (CGP) is increasingly being integrated into standard clinical practice as a strategy to guide subsequent treatment decisions by identifying novel therapeutic options based on tumor-specific mutations. However, its clinical utility in neuroendocrine neoplasms (NENs) remains to be determined. We conducted a cross-sectional analysis of genomic alterations, including tumor mutational burden (TMB) and microsatellite instability (MSI), in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), comparing neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs).
View Article and Find Full Text PDFEndocr Pathol
July 2025
Department of Pathology, University Hospitals Cleveland, Case Western Reserve University, Institute of Pathology, 11100 Euclid Avenue, Room 204, Cleveland, OH, USA.
Delta-like protein 3 (DLL3), a Notch ligand, has been identified in high-grade small- and large-cell lung carcinomas and prostate neuroendocrine carcinomas (NECs). SEZ6 (Seizure-related 6 homolog), a membrane-associated protein, has also been identified neuroendocrine neoplasms (NENs). Both DLL3 and SEZ6 are targets of novel antibody-drug conjugates (ADCs).
View Article and Find Full Text PDFSurg Case Rep
July 2025
Department of Gastrointestinal Surgery, Saitama Cancer Center, Kita-adachi-gun, Saitama, Japan.
Introduction: Gastric neuroendocrine carcinoma (G-NEC) is a rare but highly aggressive malignancy that often presents with distant metastases and significantly worsens prognosis. Recent studies have suggested that conversion surgery after chemotherapy may improve outcomes in initially unresectable gastric cancers; however, evidence regarding its application in G-NEC remains limited. We report a rare case of advanced G-NEC with multiple liver metastases that was treated with R0 resection through conversion surgery after chemotherapy.
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