TP53 mutation and immunohistochemical p53 expression characteristics in diffuse large B-cell lymphoma

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Diffuse large B-cell lymphoma (DLBCL) with TP53 mutations presents unique features and a generally poor prognosis.
• TP53 gene mutations often result in abnormal p53 protein expression patterns.

Purpose of the Study:

• To investigate the clinicopathological features and prognostic implications of TP53 mutations in DLBCL.
• To evaluate the utility of p53 protein expression, detected by immunohistochemistry (IHC), as a surrogate marker for TP53 mutation status and treatment response.

Main Methods:

• Analysis of TP53 mutation sites in 123 DLBCL patients.
• Detection of p53 protein expression levels using IHC.
• Correlation of mutation status and protein expression with clinical outcomes, including complete remission (CR) and objective response rate (ORR) following R-CHOP therapy.
• Receiver operating characteristic (ROC) curve analysis to establish cut-off values for high p53 expression.

Main Results:

• TP53 mutations were identified in 35.8% of DLBCL patients, predominantly in the DNA-binding domain.
• High p53 expression or p53 negativity (<1%) by IHC correlated with mutant-type p53 protein.
• The mutant-type p53 protein group showed significantly lower CR (50%) and ORR (75%) rates compared to the wild-type group (CR 75.86%, ORR 89.66%) after R-CHOP.
• Mutant-type p53 protein group exhibited common gene mutations in pathways like epigenetics and B cell receptor signaling.

Conclusions:

• IHC analysis of p53 protein expression is a cost-effective and straightforward method to predict TP53 mutation status in DLBCL.
• p53 protein expression levels can serve as an indicator of therapeutic response to R-CHOP chemotherapy in DLBCL patients.
• Identifying TP53 mutation status through p53 protein expression aids in understanding DLBCL's complex molecular landscape and guiding treatment strategies.