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

Whether TP53 mutation can serve as a simplified prognostic surrogate for complex genomic classifiers in diffuse large B-cell lymphoma (DLBCL) remains unclear. we comprehensively analyzed a retrospective cohort of 444 newly diagnosed DLBCL patients. TP53 mutation was an independent prognostic factor for inferior overall survival (OS) and progression-free survival (PFS) (both P < 0.001), correlating with inferior response to R-CHOP and enrichment in refractory/relapsed disease. Furthermore, multivariate analysis revealed that the adverse prognostic effect of TP53 mutation was predominantly driven by its impact within the germinal center B-cell-like (GCB) subtype, as evidenced by a significant statistical interaction. Notably, the combination of TP53 mutation and double-expression lymphoma (DEL) identified an ultra-high-risk group with synergistic poor survival. The prognostic impact was not modified by the specific protein domain, mutation burden, or gain- versus loss-of-function nature of the mutations. However, a high variant allele frequency (VAF) ≥ 53% identified a subgroup with worse survival. Finally, we adapted a p53 immunohistochemical classification from ovarian/endometrial cancer to enhance TP53 mutation prediction: overexpression (> 80%) or complete absence (< 1%) as high-risk, and heterogeneity (1%-80%) as low-risk. This approach achieved 72.5% sensitivity and 97.4% specificity, with specificity surpassed conventional ≥ 50% cutoff (P < 0.001). In conclusion, TP53 mutation is a critical, context-dependent biomarker in DLBCL, and its combination with DEL identifies a clinically actionable, ultra-high-risk group. The p53 IHC classifier shows promise as a rapid screening tool, warranting further validation.