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

Dinja T Kruger, Mark Opdam, Joyce Sanders, Vincent van der Noort, Epie Boven, Sabine C Linn

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)298-307
Number of pages10
JournalAPMIS. Acta Pathologica, Microbiologica et Immunologica Scandinavica
Issue number4
Early online date24 Jan 2020
Publication statusPublished - 1 Apr 2020


  • Breast cancer intrinsic subtypes
  • HER2-positive breast cancer
  • hierarchical clustering
  • mitogen-activated protein kinase
  • phosphatidylinositol-3-kinase
  • triple-negative breast cancer

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