Aberrant p53 immunostaining patterns in breast carcinoma of no special type strongly correlate with presence and type of TP53 mutations.
PIK3CA
TP53 mutation
Breast cancer
Immunohistochemistry
NGS
P53
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
27 Aug 2024
27 Aug 2024
Historique:
received:
08
07
2024
accepted:
12
08
2024
revised:
07
08
2024
medline:
28
8
2024
pubmed:
28
8
2024
entrez:
27
8
2024
Statut:
aheadofprint
Résumé
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 < 0.001). p53 IHC may provide a useful screening tool for identifying TP53-mutated BC of NST.
Identifiants
pubmed: 39191994
doi: 10.1007/s00428-024-03897-3
pii: 10.1007/s00428-024-03897-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 409474577
Informations de copyright
© 2024. The Author(s).
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