Early identification of TP53 mutations and TP53 allelic state in myelodysplastic neoplasms and acute myeloid leukemia via point‐of‐care p53 immunohistochemistry

Abstract Background The prolonged turnaround time for next‐generation sequencing (NGS) results may be a barrier to the timely selection of therapeutics in myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) with mutated TP53 . Biomarker validation for early detection of TP53 mutation may have a significant impact on clinical decision‐making. Methods In this study, p53 immunohistochemistry (IHC) (index test) and TP53 NGS (referent test) were performed on 145 bone marrow specimens from 82 unique patients with TP53 ‐mutant MDS or AML to validate IHC as an early surrogate for NGS, and to assess the prognostic relevance of IHC. Results p53 IHC testing was able to correctly identify 95.5% of patients with TP53 ‐mutant MDS and 100% of patients with TP53 ‐mutant AML in this cohort. The mean p53 stain positivity was higher for AML compared to MDS (28% ± 3.67% vs. 8.8% ± 1.61%; p < .001), as well as for multihit TP53 compared to monoallelic TP53 . Bootstrap analysis with 2000 iterations showed that a p53 IHC of 7% was the threshold best associated with multihit TP53 . False‐negative results were obtained with IHC in all TP53 sole nonsense or frameshift mutations. IHC positivity was inversely correlated with overall survival (OS), with the highest quintile of p53 positivity showing a median OS of just 2.53 months. Conclusions IHC is a useful biomarker for the early detection of TP53 ‐mutant MDS or AML and for prediction of TP53 allelic state. The results suggest a role for IHC across global markets, especially in geographic areas with inaccessibility to NGS testing.