Correlation of TP53 Genetic Alterations with p53 Immunohistochemical Expression and Their Prognostic Significance in DLBCL

作者：Chen Chen, Zijuan Hu, Min Ren, Longlong Bao, Ran Wei, Tian Tian, Xiaoli Zhu, Qianming Bai, Baohua Yu, Xiaoqiu Li, Xiaoyan Zhou · 发表于：Current Oncology · 年份：2025 · DOI：10.3390/curroncol32090488 · 被引用次数：3 · 研究领域：Lymphoma Diagnosis and Treatment、Viral-associated cancers and disorders、CNS Lymphoma Diagnosis and Treatment

TP53 genetic alterations represent a critical molecular feature in diffuse large B-cell lymphoma (DLBCL), with well-established associations with aggressive disease behavior and therapeutic resistance. However, significant controversy persists regarding the clinical utility of p53 immunohistochemical (IHC) expression as a surrogate marker. This study presents a thorough investigation of TP53 genetic alterations and their correlation with p53 protein expression in 664 cases of DLBCL. Using targeted next-generation sequencing (tNGS), we identified TP53 alterations (mutations and/or copy number losses (CNLs)) in 170 cases (25.6%). Among them, 161 cases had mutations. Concurrent analysis of copy number variations (CNVs) in 109 cases revealed TP53 CNLs in 17.4% (19/109), with 68.4% (13/19) of these showing coexisting mutations. Immunohistochemical evaluation of p53 expression in 371 cases demonstrated strong positivity (≥65% cells) in 21% (78/371), complete negativity (<1%) in 5.7% (21/371), and wild-type pattern (1–65%) in 73.3% (272/371) of cases. The p53 IHC laboratory-developed test (LDT) showed 79.2% sensitivity and 91.6% specificity for detecting TP53 alterations overall, though sensitivity varied significantly by mutation type: 86.2% for missense mutations but only 14.3% for nonsense mutations. Clinically, cases with TP53 alterations exhibited more aggressive disease characteristics, including higher ECOG performance scores, increased frequency of B symptoms, and poorer ...