Optimized interpretation of p53 immunohistochemistry for prediction of TP53 mutations and patient survival in DLBCL

The prognostic value of p53 immunohistochemical (IHC) staining in diffuse large B cell lymphoma (DLBCL) remains controversial. We retrospectively included 149 patients who were diagnosed with and treated for DLBCL at Peking Union Medical College Hospital (PUMCH). TP53 IHC staining and TP53 sequencing was performed from paraffin-embedded biopsy tissues. Clinical information including basic characteristics and outcome was collected for data analysis. An internal validation cohort of 58 patients with DLBCL was also retrospectively recruited in PUMCH. In the 149 DLBCL cohort, TP53 mutations were detected in 40 patients, with 29 harboring damaging mutations. TP53 mutation showed no significant correlation with either PFS (p = 0.065) or OS (p = 0.140), whereas damaging TP53 mutations were significantly correlated with poor PFS (p = 0.008) and OS (p = 0.030). A novel P53 IHC reading pattern was identified. Using the percentage of cells with strong p53 intensity (p53str) as IHC readout, we discovered a significant correlation of high p53str staining (p53strhigh) with TP53 damaging mutation (p = 0.001). Importantly, p53strhigh was significantly correlated with poorer PFS (p < 0.001) and OS (p = 0.001). The estimated 5-year PFS and 5-year OS rates were 58.8% and 74.3% for p53strlow, and 17.9% (p = 0.001) and 30.1% (p < 0.001) for p53strhigh. Incorporating p53str into the IPI score significantly improved risk stratification of DLBCL. An internal validation cohort of 58 DLBCL patients confirmed the prognostic value of p53str. These results indicate p53str as a promising readout for p53 IHC staining and support its role as a surrogate marker for TP53 mutations and patient survival in DLBCL.