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<p>Whether&#xa0;<i>TP53</i>&#xa0;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. <i>TP53</i> mutation was an independent prognostic factor for inferior overall survival (OS) and progression-free survival (PFS) (both <i>P</i> &lt; 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&#xa0;<i>TP53</i>&#xa0;mutation was&#xa0;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 <i>TP53</i> 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.&#xa0;Finally, we adapted a p53 immunohistochemical classification from ovarian/endometrial cancer to enhance <i>TP53</i> mutation prediction: overexpression (&gt; 80%) or complete absence (&lt; 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 (<i>P</i> &lt; 0.001). In conclusion, <i>TP53</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月29日

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  • Haiyan Zhang,
  • Xiang Zhang,
  • Jinghan Wang,
  • Xuewu Zhang,
  • Yunfei Lv,
  • Yanan Zhu,
  • Xingnong Ye,
  • Juying Wei,
  • Min Yang,
  • Gaixiang Xu,
  • Chunmei Yang,
  • Haitao Meng,
  • Wanzhuo Xie,
  • Jie Jin,
  • Hongyan Tong,
  • Wenjuan Yu

摘要

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.