Evaluating murine double minute 2 status as a stratification tool for risk-adapted management in plasma cell...

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.

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.

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.

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.

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.