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Hierarchical clustering of PI3K and MAPK pathway proteins in breast cancer intrinsic subtypes
Author(s) -
Kruger Dinja T.,
Opdam Mark,
Sanders Joyce,
Noort Vincent,
Boven Epie,
Linn Sabine C.
Publication year - 2020
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.13026
Subject(s) - breast cancer , pi3k/akt/mtor pathway , pten , immunohistochemistry , mapk/erk pathway , cancer research , protein kinase b , cancer , medicine , kinase , protein kinase a , metastatic breast cancer , phosphorylation , signal transduction , biology , microbiology and biotechnology
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.