Ebrahim NAA, Othman MO, Tahoun NS, Salama RA, Arafat A, Amin NH. Deciphering prognostic markers in gastric signet ring cell carcinoma: Human epidermal growth factor receptor 2 and other key factors. World J Clin Oncol 2025; 16(8): 107987 [DOI: 10.5306/wjco.v16.i8.107987]
Corresponding Author of This Article
Noura Atef A Ebrahim, MD, PhD, Postdoc, Assistant Professor, Consultant, Post Doctoral Researcher, Department of Oncologic Pathology, National Cancer Institute, Cairo University, Fom El-Khalig Street, Cairo 11796, Egypt. npathologist@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Aug 24, 2025; 16(8): 107987 Published online Aug 24, 2025. doi: 10.5306/wjco.v16.i8.107987
Deciphering prognostic markers in gastric signet ring cell carcinoma: Human epidermal growth factor receptor 2 and other key factors
Noura Atef A Ebrahim, Moamen O Othman, Neveen S Tahoun, Rasha A Salama, Aya Arafat, Nancy H Amin
Noura Atef A Ebrahim, Neveen S Tahoun, Nancy H Amin, Department of Oncologic Pathology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
Moamen O Othman, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 11562, Egypt
Rasha A Salama, Department of Community Medicine, Ras Al Khaimah Medical and Health Science University, Ras Al Khaimah 11172, United Arab Emirates
Aya Arafat, Department of Clinical and Chemical Pathology, Kasr Al-Aini faculty of Medicine, Cairo University, Cairo 11562, Egypt
Author contributions: Ebrahim NAA designed the study, conducted histopathological and immunohistochemical examinations,was responsible for data collection and data interpretation, and drafted the manuscript; Othman MO assisted in data collection; Tahoun NS provided valuable guidance and reviewed the manuscript; Salama RA and Arafat A offered clinical insights; Othman MO, Arafat A, and Salama RA contributed to the manuscript revisions; Amin NH supported the histological examinations and contributed to the immunohistochemistry analysis; Salama RA, Arafat A, and Amin NH contributed to data interpretation; all authors approved the final version to publish.
Institutional review board statement: This study is approved by Cairo University National Cancer Institute Institutional Review Board, No. PA2502-501-092-196.
Informed consent statement: Due to the retrospective nature of the study, Cairo University National Cancer Institute Institutional Review Board waived the need of obtaining informed consent.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request at npathologist@gmail.com.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Noura Atef A Ebrahim, MD, PhD, Postdoc, Assistant Professor, Consultant, Post Doctoral Researcher, Department of Oncologic Pathology, National Cancer Institute, Cairo University, Fom El-Khalig Street, Cairo 11796, Egypt. npathologist@gmail.com
Received: April 2, 2025 Revised: April 29, 2025 Accepted: June 18, 2025 Published online: August 24, 2025 Processing time: 140 Days and 15.8 Hours
Abstract
BACKGROUND
Gastric signet ring cell carcinoma (SRCC) is a rare, aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior. Despite advances in gastric cancer treatment, SRCC remains difficult to diagnose early and manage effectively due to its infiltrative pattern and molecular variability. Reliable prognostic markers are critical to guide clinical management.
AIM
To investigate the prognostic factors, including human epidermal growth factor receptor 2 (HER2) expression, associated with survival outcomes in patients with gastric SRCC.
METHODS
A retrospective analysis of 100 cases diagnosed between 2015 and 2019 was conducted, assessing demographic, clinical, and pathological data. HER2 expression was analyzed using immunohistochemistry, and survival outcomes, including overall survival and disease-free survival, were examined.
RESULTS
With a median follow-up of 43 months, the median patient age was 50 years, and males exhibited a higher mortality rate (P = 0.0107). Elevated serum carbohydrate antigen 19-9 and carcinoembryonic antigen levels were significantly associated with increased mortality (P = 0.00149 and P = 0.00163, respectively). Advanced tumor-node-metastasis stage and lymphovascular invasion were strong predictors of poor outcomes (P < 0.001 and P = 0.019). HER2 positivity correlated with higher mortality (P = 0.00882) but was not significantly linked to recurrence (P = 0.53). Surgical treatment significantly improved survival compared with non-surgical approaches (P = 0.0226).
CONCLUSION
These findings highlight the aggressive nature of SRCC with advanced disease stage, elevated tumor markers, and lymphovascular invasion contributing to poor outcomes. HER2 expression, though infrequent, may indicate worse prognosis, reinforcing the role of surgical intervention in survival improvement.
Core Tip: This study provided a comprehensive analysis of gastric signet ring cell carcinoma, emphasizing its unique histopathological features, clinical implications, and prognostic significance. By examining key tumor characteristics, including infiltration patterns and molecular alterations, the research highlighted the challenges in early diagnosis and treatment. The findings contributed to a deeper understanding of the aggressive nature of signet ring cell carcinoma and its impact on patient outcomes, underscoring the need for improved diagnostic strategies and targeted therapeutic approaches.
