TP53 mutation predict poor prognosis in diffuse large B-cell lymphoma: a single-center study.

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• The prognostic value of TP53 mutations in diffuse large B-cell lymphoma (DLBCL) compared to complex genomic classifiers is not fully understood.
• TP53 mutations are implicated in various cancers, but their specific role in DLBCL subtypes requires further elucidation.

Purpose of the Study:

• To investigate TP53 mutation as a prognostic biomarker in DLBCL.
• To evaluate the impact of TP53 mutation on treatment response and survival outcomes.
• To explore the utility of a p53 immunohistochemical (IHC) classifier for predicting TP53 mutation status.

Main Methods:

• Comprehensive genomic analysis of 444 newly diagnosed DLBCL patients.
• Multivariate analysis to assess the prognostic significance of TP53 mutations.
• Correlation analysis between TP53 mutation status, treatment response (R-CHOP), and clinical outcomes (OS, PFS).
• Adaptation and validation of a p53 IHC classification system.

Main Results:

• TP53 mutation is an independent predictor of inferior overall survival (OS) and progression-free survival (PFS) in DLBCL patients (P < 0.001).
• The adverse prognostic effect of TP53 mutation is more pronounced in the germinal center B-cell-like (GCB) subtype.
• Combination of TP53 mutation and double-expression lymphoma (DEL) identifies an ultra-high-risk group with significantly poorer survival.
• A p53 IHC classifier demonstrated high sensitivity (72.5%) and specificity (97.4%) for predicting TP53 mutation status, outperforming conventional cutoffs.

Conclusions:

• TP53 mutation is a critical, context-dependent biomarker in DLBCL.
• The combination of TP53 mutation and DEL defines a clinically actionable ultra-high-risk subgroup.
• The p53 IHC classifier shows potential as a rapid and accurate screening tool for TP53 mutation status in DLBCL.