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Aberrant p53 immunostaining patterns in breast carcinoma of no special type strongly correlate with presence and type of TP53 mutations

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Názov: Aberrant p53 immunostaining patterns in breast carcinoma of no special type strongly correlate with presence and type of TP53 mutations
Autori: Hannes Armbruster, Tilman Schotte, Isabell Götting, Mathis Overkamp, Massimo Granai, Lea Louise Volmer, Veronika Bahlinger, Sabine Matovina, André Koch, Dominik Dannehl, Tobias Engler, Andreas D. Hartkopf, Sara Y. Brucker, Irina Bonzheim, Falko Fend, Annette Staebler, Ivonne Montes-Mojarro
Zdroj: Virchows Arch
Informácie o vydavateľovi: Springer Science and Business Media LLC, 2024.
Rok vydania: 2024
Predmety: Adult, Aged, 80 and over, 0301 basic medicine, Female [MeSH], Immunohistochemistry, Mutation [MeSH], Aged, 80 and over [MeSH], P53, Aged [MeSH], Adult [MeSH], Receptor, ErbB-2/metabolism [MeSH], Humans [MeSH], Breast Neoplasms/genetics [MeSH], Breast cancer, Receptor, ErbB-2/genetics [MeSH], Middle Aged [MeSH], Tumor Suppressor Protein p53/genetics [MeSH], DNA Mutational Analysis [MeSH], Receptor, ErbB-2/analysis [MeSH], Immunohistochemistry [MeSH], Original Article, NGS, Tumor Suppressor Protein p53/analysis [MeSH], Class I Phosphatidylinositol 3-Kinases/genetics [MeSH], Biomarkers, Tumor/genetics [MeSH], Biomarkers, Tumor/analysis [MeSH], Breast Neoplasms/pathology [MeSH], Class I Phosphatidylinositol 3-Kinases, Receptor, ErbB-2, DNA Mutational Analysis, Breast Neoplasms, Middle Aged, 03 medical and health sciences, 0302 clinical medicine, Mutation, Biomarkers, Tumor, Humans, Female, Tumor Suppressor Protein p53, Aged
Popis: Recent 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 TP53-mutated BC of NST.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1432-2307
0945-6317
DOI: 10.1007/s00428-024-03897-3
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39191994
https://repository.publisso.de/resource/frl:6495453
Rights: CC BY
Prístupové číslo: edsair.doi.dedup.....dac89b1276630aac8292da6cebbb9c47
Databáza: OpenAIRE
Popis
Abstrakt:Recent 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 TP53-mutated BC of NST.
ISSN:14322307
09456317
DOI:10.1007/s00428-024-03897-3