Dr Gerber on the Benefits of p53 IHC Testing for Identifying TP53-Mutant MDS and AML in Underserved Regions

"Within the United States, in some of our more underserved and rural areas where there might not be ready access both to the expertise with NGS and NGS testing [itself], this is a relatively simple, straightforward assay. Hopefully, this [tool] can expedite early referral and facilitate early referral to transplant-capable centers."

Jonathan M. Gerber, MD, a member of the faculty in the Department of Medicine at New York University (NYU) Grossman School of Medicine; as well as the chief clinical officer of the NYU Perlmutter Cancer Center, discussed the potential for implementing p53 immunohistochemistry (IHC) testing as a cost-effective alternative to next-generation sequencing (NGS) in regions with limited molecular diagnostic resources.

Findings from a recent analysis led by Gerber and colleagues suggest that IHC-based stratification may serve as a viable method for identifying high-risk patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) who harbor multi-hit TP53 mutations, Gerber began.

In the study, a p53 IHC positivity threshold of 7% was found to best correlate with multi-hit TP53 mutational status in a cohort of 82 patients with concurrent IHC and NGS data. Higher IHC positivity was also associated with worse overall survival, reinforcing the prognostic relevance of this metric. Notably, false-negative IHC results were observed exclusively in cases involving sole nonsense or frameshift TP53 mutations, suggesting limitations in IHC sensitivity for detecting certain mutational subtypes.

Gerber emphasized the practical value of p53 IHC in underserved or rural settings, where access to comprehensive NGS testing and hematopathology expertise may be limited. As a widely available and relatively simple assay, IHC could help expedite early risk stratification and referral to transplant-capable centers. He also noted the potential for artificial intelligence to support automated interpretation and standardization of IHC results, which could further increase its scalability and reliability in community settings.

Importantly, IHC provides functional insights into p53 protein behavior—such as abnormal localization or intensity of staining—that may not be directly inferred from DNA-level sequencing alone, Gerber noted. This added layer of information could help clinicians identify candidates for clinical trials investigating therapies for TP53-mutated disease, particularly given the poor prognosis and limited treatment options associated with high-burden TP53 alterations. Early molecular characterization using accessible tools such as p53 IHC could therefore facilitate timely trial enrollment and improve care pathways in MDS and AML, Gerber concluded.