AJHE2405 - CME/CMLE - p53 immunohistochemistry as an ancillary tool for rapid assessment of residual disease in TP53-mutated acute myeloid leukemia and myelodysplastic syndromes-p53 immunohistochemistry as an ancillary tool for rapid assessment of residual disease in TP53-mutated acute myeloid leukemia and myelodysplastic syndromes

p53 immunohistochemistry as an ancillary tool for rapid assessment of residual disease in TP53-mutated acute myeloid leukemia and myelodysplastic syndromes

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The article outlines a study on the use of p53 immunohistochemistry (IHC) as an ancillary tool for detecting residual disease in patients with TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) post-therapy. The effectiveness of traditional methods like measurable residual disease flow cytometry (MRD-FC) and next-generation sequencing (NGS) is often hindered by low sensitivity in suboptimal bone marrow aspirates or when neoplastic blasts mimic normal cells. The study investigates whether p53 IHC, indicative of TP53 mutation, can improve detection under these challenging conditions.<br /><br />Key findings from the retrospective analysis of 28 bone marrow samples from nine patients reveal that p53 IHC detects residual disease with 94% sensitivity and 89% specificity when using a threshold of more than ten 2-3 positive cells per 400 high-power field. This high concordance rate was confirmed by multiple pathologists, indicating reliable reproducibility.<br /><br />The study posits that p53 IHC is beneficial in scenarios where MRD-FC results are equivocal or where aspirates are hampered by fibrosis or technical challenges, thereby offering a rapid (within 24 hours) and effective complement to MRD-FC and NGS. Despite its promising utility, p53 IHC’s application is limited to TP53-mutated cases with high nuclear p53 expression established during initial diagnosis.<br /><br />The research draws on previous findings that illustrate high p53 protein levels correlate with TP53 mutations and poor patient prognosis, emphasizing the importance of accurate residual disease detection for patient management and prognosis. The study’s results have significant implications for clinical practice, suggesting p53 IHC as a potent tool to aid effective and timely detection of residual disease in TP53-mutated AML/MDS cases where traditional methods fall short.

Keywords

p53 immunohistochemistry

TP53-mutated

acute myeloid leukemia

myelodysplastic syndromes

residual disease detection

measurable residual disease flow cytometry

next-generation sequencing

bone marrow aspirates

sensitivity and specificity

clinical practice implications