Jin Yiping, Wang Yi, Wang Lu, Zhang He, Ren Beibei, Zheng Jiawen, Xia Qingxin, Liu Yanyan
Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China.
Department of Molecular pathology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China.
Front Oncol. 2025 Apr 28;15:1550207. doi: 10.3389/fonc.2025.1550207. eCollection 2025.
Diffuse large B-cell lymphoma (DLBCL) with TP53 mutations has specific clinicopathological features and is usually associated with a poor prognosis. TP53 gene mutations typically lead to aberrant expression patterns of the p53 protein. We studied 123 DLBCL patients at Henan Cancer Hospital, 35.8% (44/123) had TP53 mutations. Analysis of mutation sites in 44 cases of DLBCL patients revealed that the mutations primarily occur in the DNA-binding domain (DBD region) of the encoded p53 protein; among all mutation types, there were 8 truncation or frameshift mutations, and 36 missense mutations. Further, immunohistochemistry (IHC) detected expression levels of p53 protein in 123 DLBCL samples. The mutation results were used as a reference, and receiver operating characteristic (ROC) curve analysis was employed. Ultimately, the expression ratio of 65% and the moderate-strong expression intensity were regarded as the cut-off value, namely high p53 expression or p53 negative (<1%) indicated mutant-type p53 protein. the complete remission (CR) rate of the mutant-type p53 protein group after receiving R-CHOP regimen was 50% (14/28), and the objective response rate (ORR) was 75%, which differed significantly (P<0.01) compared with wild-type p53 protein group [CR rate of 75.86% (66/87) and ORR rate of 89.66%]. Common gene mutations in the mutant-type p53 protein group primarily involve alterations in pathways related to epigenetics, B cell antigen receptor signaling, cell cycle, among others. IHC analysis of the p53 protein is a simple and low-cost approach that can be employed to predict TP53 mutation status and therapy response.
具有TP53突变的弥漫性大B细胞淋巴瘤（DLBCL）具有特定的临床病理特征，通常预后较差。TP53基因突变通常导致p53蛋白异常表达模式。我们对河南肿瘤医院的123例DLBCL患者进行了研究，35.8%（44/123）存在TP53突变。对44例DLBCL患者的突变位点分析显示，突变主要发生在编码的p53蛋白的DNA结合域（DBD区域）；在所有突变类型中，有8个截断或移码突变，36个错义突变。此外，免疫组织化学（IHC）检测了123例DLBCL样本中p53蛋白的表达水平。以突变结果为参照，采用受试者工作特征（ROC）曲线分析。最终，将65%的表达率和中等-强表达强度作为截断值，即p53高表达或p53阴性（<1%）表明为突变型p53蛋白。接受R-CHOP方案后，突变型p 53蛋白组的完全缓解（CR）率为50%（14/28），客观缓解率（ORR）为75%，与野生型p53蛋白组相比差异有统计学意义（P<0.01）[CR率为75.86%（66/87），ORR率为89.66%]。突变型p53蛋白组常见的基因突变主要涉及表观遗传学、B细胞抗原受体信号传导、细胞周期等相关途径的改变。p53蛋白的IHC分析是一种简单且低成本的方法，可用于预测TP53突变状态和治疗反应。
