Ebrahim NAA, Elfandy H, Arafat AMA, Darwish AD, Eltohamy MI. Evaluating murine double minute 2 status as a stratification tool for risk-adapted management in plasma cell neoplasms. World J Clin Oncol 2026; 17(1): 111426 [DOI: 10.5306/wjco.v17.i1.111426]
Corresponding Author of This Article
Noura A A Ebrahim, MD, MSc, PhD, Assistant Professor, Department of Oncologic Pathology, National Cancer Institute, Cairo University, 1st Kasr Alainy Street, Cairo 11796, Al Qāhirah, Egypt. npathologist@gmail.com
Research Domain of This Article
Pathology
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. Jan 24, 2026; 17(1): 111426 Published online Jan 24, 2026. doi: 10.5306/wjco.v17.i1.111426
Evaluating murine double minute 2 status as a stratification tool for risk-adapted management in plasma cell neoplasms
Noura A A Ebrahim, Habiba Elfandy, Aya Mohamed Adel Arafat, Amira Diyaa Darwish, Mahitab Ibrahim Eltohamy
Noura A A Ebrahim, Habiba Elfandy, Mahitab Ibrahim Eltohamy, Department of Oncologic Pathology, National Cancer Institute, Cairo University, Cairo 11796, Al Qāhirah, Egypt
Aya Mohamed Adel Arafat, Department of Clinical and Chemical Pathology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 11562, Egypt
Amira Diyaa Darwish, Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo 11796, Al Qāhirah, Egypt
Co-first authors: Noura A A Ebrahim and Habiba Elfandy.
Author contributions: Ebrahim NAA and Elfandy H contributed equally to this manuscript and are co-first authors. All authors made equal and substantial contributions to the conception, design, data analysis, and writing of the manuscript. Each author has reviewed and approved the final version and agrees to be accountable for all aspects of the work.
Institutional review board statement: This investigation was carried out following the ethical principles stated in the Declaration of Helsinki. Ethical approval was granted by the Institutional Review Board of the National Cancer Institute, Cairo University, Approval No. PA2505-506-104-199.
Informed consent statement: As the study was retrospective and utilized anonymized data, the IRB granted a waiver for the requirement of informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement:
The datasets generated or analyzed during the current study are available from the corresponding author upon reasonable request.
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 A A Ebrahim, MD, MSc, PhD, Assistant Professor, Department of Oncologic Pathology, National Cancer Institute, Cairo University, 1st Kasr Alainy Street, Cairo 11796, Al Qāhirah, Egypt. npathologist@gmail.com
Received: July 7, 2025 Revised: July 29, 2025 Accepted: December 11, 2025 Published online: January 24, 2026 Processing time: 205 Days and 10 Hours
Abstract
BACKGROUND
The E3 ubiquitin ligase murine double minute 2 (MDM2) is a key negative regulator of the tumor suppressor protein p53 and has been implicated in the development of various cancers, including hematologic malignancies. In multiple myeloma (MM), increased MDM2 expression has been reported and may play a role in disease progression and resistance to therapy. Despite this, the prognostic implications of MDM2 detected through immunohistochemistry (IHC) remain insufficiently defined.
AIM
To evaluate the clinical, pathological, and prognostic significance of MDM2 expression in plasma cell neoplasms, with a focus on its potential utility as an early indicator of disease severity and therapeutic response.
METHODS
A retrospective analysis was conducted on 71 patients diagnosed with MM or related plasma cell disorders treated at the National Cancer Institute between 2018 and 2022. MDM2 protein expression was assessed using IHC on extramedullary lesion biopsy samples, employing the MDM2 (A.M.1) monoclonal antibody. Nuclear staining in at least 1% of plasma cells was used as the threshold for MDM2 positivity. Comparative analyses were performed between MDM2-positive and MDM2-negative groups, examining clinical characteristics, laboratory data, histopathological features, treatment responses at 12 weeks and 24 weeks, and survival outcomes, including relapse-free survival (RFS) and overall survival.
RESULTS
MDM2 expression was identified in 30% of patient samples. While no major differences were observed in baseline demographics, disease stage, or most laboratory values, serum albumin levels were significantly lower in MDM2-positive patients (P = 0.007). At 12 weeks, patients with MDM2-positive disease showed significantly poorer treatment responses based on International Myeloma Working Group criteria (P = 0.002), and early clinical response was moderately negatively correlated with MDM2 expression (Spearman’s P = 0.375, P = 0.001). This correlation was not observed at 24 weeks. Immunophenotypic analysis indicated that MDM2-positive plasma cells exhibited lower epithelial membrane antigen (P = 0.014) and higher CD45 expression (P = 0.039), suggesting altered differentiation. Kaplan-Meier survival analysis demonstrated a markedly shorter median RFS in the MDM2-positive group (22 months vs 68 months, P < 0.001), although no significant difference was found in overall survival.
CONCLUSION
IHC-detected MDM2 overexpression identifies a distinct subset of plasma cell neoplasms characterized by reduced early treatment responsiveness and significantly shorter RFS. These findings support the potential of MDM2 as a prognostic biomarker for early relapse risk in MM. Incorporating MDM2 assessment into diagnostic and prognostic workflows may enable more individualized treatment approaches. Further validation through prospective studies is recommended.
Core Tip: This research explores the prognostic significance of murine double minute 2 (MDM2) expression in plasma cell neoplasms, with particular attention to plasmacytomas. The findings reveal a distinct subset of patients with MDM2 positivity who demonstrate poorer early treatment responses and markedly shorter relapse-free survival intervals. Incorporating MDM2 expression into contemporary prognostic frameworks could enhance individualized treatment planning for those with multiple myeloma. Overall, the evidence indicates that MDM2 functions as both a marker of aggressive tumor biology and a promising indicator for early-stage risk stratification, supporting more vigilant follow-up and personalized therapeutic intervention to reduce relapse likelihood.
