Gastric carcinoma harbouring loss‑of‑function mutations in the PIK3R1, ATRX and RBM10 genes exhibits diverse histological features associated with EBV infection and TP53 inactivation: A case report

Jeong,Se Un; Choi,Euno; Kim,Yongil; Byeon,Jaeyoung; Kim,So-Woon

doi:10.3892/ol.2025.15002

Gastric carcinoma harbouring loss‑of‑function mutations in the PIK3R1, ATRX and RBM10 genes exhibits diverse histological features associated with EBV infection and TP53 inactivation: A case report

Authors:
- Se Un Jeong
- Euno Choi
- Yongil Kim
- Jaeyoung Byeon
- So-Woon Kim
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Affiliations: Department of Pathology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Republic of Korea, Department of Pathology, Ewha Woman's University Mokdong Hospital, Ewha Woman's University College of Medicine, Seoul 07985, Republic of Korea, Department of Surgery, Ewha Woman's University Mokdong Hospital, Ewha Woman's University College of Medicine, Seoul 07985, Republic of Korea, LabGenomics Clinical Research Institute, LabGenomics, Seongnam, Gyeonggi 13488, Republic of Korea
Published online on: April 1, 2025 https://doi.org/10.3892/ol.2025.15002
Article Number: 256
Copyright: © Jeong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

This study presents a novel case of gastric carcinoma (GC) with diverse histological features and unique molecular alterations. A 62‑year‑old man with hematemesis was diagnosed with advanced GC and hepatic metastasis. Despite palliative gastrectomy to control bleeding, the patient succumbed within 6 months. Histological examination revealed three distinct tumour components: Gastric adenosquamous carcinoma (GASC), GC with lymphoid stroma (GCLS) and poorly differentiated adenocarcinoma (PDAD). Immunohistochemical staining, next‑generation sequencing and Epstein‑Barr virus (EBV) in situ hybridisation were performed to characterise the tumour. The GASC component revealed diffuse p40 and p63 immunoreactivity, while the GCLS and PDAD components were negative for both markers. All components harboured a missense mutation in the phosphoinositide‑3‑kinase regulatory subunit 1 gene and deletions in the ATRX and RNA binding motif protein 10 genes. Additionally, the GCLS component was EBV positive and the PDAD component demonstrated concurrent EBV infection and TP53 inactivation. The present case highlights the importance of thorough molecular and histological evaluation, as distinct molecular alterations and heterogenous EBV status in histologically diverse components may significantly influence patient prognosis and treatment strategies.

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