{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T14:31:04Z","timestamp":1783780264315,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:00Z","timestamp":1750464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The prolonged turnaround time for next\u2010generation sequencing (NGS) results may be a barrier to the timely selection of therapeutics in myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) with mutated <jats:italic>TP53<\/jats:italic>. Biomarker validation for early detection of <jats:italic>TP53<\/jats:italic> mutation may have a significant impact on clinical decision\u2010making.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, p53 immunohistochemistry (IHC) (index test) and <jats:italic>TP53<\/jats:italic> NGS (referent test) were performed on 145 bone marrow specimens from 82 unique patients with <jats:italic>TP53<\/jats:italic>\u2010mutant MDS or AML to validate IHC as an early surrogate for NGS, and to assess the prognostic relevance of IHC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>p53 IHC testing was able to correctly identify 95.5% of patients with <jats:italic>TP53<\/jats:italic>\u2010mutant MDS and 100% of patients with <jats:italic>TP53<\/jats:italic>\u2010mutant AML in this cohort. The mean p53 stain positivity was higher for AML compared to MDS (28%\u00a0\u00b1\u00a03.67% vs. 8.8%\u00a0\u00b1\u00a01.61%; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001), as well as for multihit <jats:italic>TP53<\/jats:italic> compared to monoallelic <jats:italic>TP53<\/jats:italic>. Bootstrap analysis with 2000 iterations showed that a p53 IHC of 7% was the threshold best associated with multihit <jats:italic>TP53<\/jats:italic>. False\u2010negative results were obtained with IHC in all <jats:italic>TP53<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IHC is a useful biomarker for the early detection of <jats:italic>TP53<\/jats:italic>\u2010mutant MDS or AML and for prediction of <jats:italic>TP53<\/jats:italic> allelic state. The results suggest a role for IHC across global markets, especially in geographic areas with inaccessibility to NGS testing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35950","type":"journal-article","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T09:40:02Z","timestamp":1750498802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Early identification of <i>TP53<\/i> mutations and <i>TP53<\/i> allelic state in myelodysplastic neoplasms and acute myeloid leukemia via point\u2010of\u2010care p53 immunohistochemistry"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8208-1902","authenticated-orcid":false,"given":"Shyam A.","family":"Patel","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology Department of Medicine UMass Memorial Medical Center UMass Chan Medical School  Worcester Massachusetts USA"},{"name":"Center for Clinical and 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