Hierarchical clustering of PI3K and MAPK pathway proteins in breast cancer intrinsic subtypes.


Journal

APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
ISSN: 1600-0463
Titre abrégé: APMIS
Pays: Denmark
ID NLM: 8803400

Informations de publication

Date de publication:
Apr 2020
Historique:
received: 11 06 2019
accepted: 10 01 2020
pubmed: 25 1 2020
medline: 27 5 2020
entrez: 25 1 2020
Statut: ppublish

Résumé

The phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are frequently activated in breast cancer. We recently demonstrated the importance of analyzing multiple proteins as read-out for pathway activation in ER+/HER2- breast cancer, since single proteins are known to provide insufficient information. Here, we determined pathway activation in other primary breast cancer intrinsic subtypes derived from postmenopausal patients. Tumor blocks were recollected, and immunohistochemistry was performed using antibodies against PTEN, p-AKT(Thr308), p-AKT(Ser473), p-p70S6K, p-4EBP1, p-S6RP(Ser235/236) and p-ERK1/2, followed by unsupervised hierarchical clustering. In 32 ER+/HER2+, 37 ER-/HER2+ and 74 triple-negative breast cancer patients, subgroups were identified with preferentially activated (A) and preferentially not activated (N) proteins. These subgroups likely reflect tumors with differences in biological behavior as well as treatment outcome.

Identifiants

pubmed: 31976581
doi: 10.1111/apm.13026
pmc: PMC7317370
doi:

Substances chimiques

Biomarkers, Tumor 0
Phosphatidylinositol 3-Kinase EC 2.7.1.137
Receptor, ErbB-2 EC 2.7.10.1
Proto-Oncogene Proteins c-akt EC 2.7.11.1
Ribosomal Protein S6 Kinases, 70-kDa EC 2.7.11.1
Mitogen-Activated Protein Kinases EC 2.7.11.24

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

298-307

Subventions

Organisme : TI Pharma
ID : T3-502

Informations de copyright

© 2020 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Medical Microbiology and Pathology.

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Auteurs

Dinja T Kruger (DT)

Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam/Cancer Center Amsterdam, Amsterdam, The Netherlands.
Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Mark Opdam (M)

Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Joyce Sanders (J)

Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Vincent van der Noort (V)

Division of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Epie Boven (E)

Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam/Cancer Center Amsterdam, Amsterdam, The Netherlands.

Sabine C Linn (SC)

Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Pathology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

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