Aberrant p53 immunostaining patterns in breast carcinoma of no special type strongly correlate with presence and type of TP53 mutations
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Published:2024-08-27
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ISSN:0945-6317
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Container-title:Virchows Archiv
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language:en
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Short-container-title:Virchows Arch
Author:
Armbruster HannesORCID, Schotte Tilman, Götting Isabell, Overkamp Mathis, Granai MassimoORCID, Volmer Lea LouiseORCID, Bahlinger Veronika, Matovina SabineORCID, Koch AndréORCID, Dannehl DominikORCID, Engler TobiasORCID, Hartkopf Andreas D.ORCID, Brucker Sara Y.ORCID, Bonzheim IrinaORCID, Fend FalkoORCID, Staebler AnnetteORCID, Montes-Mojarro IvonneORCID
Abstract
AbstractRecent studies have revealed an association between TP53 mutations and endocrine resistance in hormone receptor-positive, HER2-negative breast cancer (HR + HER2 −BC). Aberrant p53 immunostaining (IHC) patterns may provide a surrogate marker for TP53 mutations. Building upon a ternary algorithm of aberrant staining patterns, this study evaluates the reliability of p53 IHC as screening tool for TP53 mutations in BC (NST). Furthermore, it describes the histopathological and molecular characteristics of TP53-mutated cases, along with the mutational status of PIK3CA. This study comprised 131 early-stage, node-negative BCs with available core biopsies and resection specimens. Cases were categorized as follows: HR + HER2 − (85 cases), HER2 + (21 cases) and triple negative (TN, 25 cases). Aberrant IHC staining patterns for p53 were defined as overexpression (OE), complete absence (CA) and cytoplasmic (CY). In addition, targeted sequencing of TP53 and PIK3CA genes was performed. TP53 mutations were identified in 53 of 126 cases (42.1%). Within HR + HER2 − cases, TP53 mutations were found in 17 of 80 cases (21.3%). IHC accurately predicted TP53 mutation in 96.2% of cases with a specificity of 100%. Additionally, there was a significant agreement between missense mutations and OE, as well as between truncating mutations and CA (κ 73% and 76%). CY was observed in two TN cases with truncating mutations within the nuclear localization signalling domain of p53. TP53-mutated cases exhibited higher grade, greater nuclear pleomorphism and higher Ki-67 proliferation index and were associated with the PIK3CA wild-type status (p < 0.001). p53 IHC may provide a useful screening tool for identifying TP53-mutated BC of NST.
Funder
Deutsche Forschungsgemeinschaft Eberhard Karls Universität Tübingen
Publisher
Springer Science and Business Media LLC
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