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

Dinja T Kruger1,2, Mark Opdam2, Joyce Sanders3

  • 1Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam/Cancer Center Amsterdam, Amsterdam, The Netherlands.

APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica
|January 25, 2020
PubMed

Insights

Analyzing multiple proteins reveals distinct phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathway activation patterns in different breast cancer subtypes. These patterns may predict tumor behavior and treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways are crucial in breast cancer development and progression.
  • Previous research highlighted the inadequacy of single protein markers for assessing pathway activation in ER+/HER2- breast cancer.

Purpose of the Study:

  • To investigate and characterize the activation status of PI3K and MAPK pathways across diverse intrinsic subtypes of primary breast cancer in postmenopausal patients.
  • To determine if analyzing multiple protein readouts can identify distinct subgroups within these subtypes.

Main Methods:

  • Immunohistochemistry was employed to assess the expression and activation levels of key proteins in the PI3K/AKT/mTOR and MAPK pathways (PTEN, p-AKT(Thr308), p-AKT(Ser473), p-p70S6K, p-4EBP1, p-S6RP(Ser235/236), p-ERK1/2).
  • Unsupervised hierarchical clustering was utilized to analyze the protein data from 32 ER+/HER2+, 37 ER-/HER2+, and 74 triple-negative breast cancer patient samples.
  • Tumor blocks from postmenopausal patients were recollected for comprehensive analysis.

Main Results:

  • Subgroups of patients with preferentially activated (A) and non-activated (N) protein profiles were identified within the ER+/HER2+, ER-/HER2+, and triple-negative breast cancer subtypes.
  • These findings suggest heterogeneity in pathway activation within different breast cancer subtypes.

Conclusions:

  • The multi-protein analysis approach reveals distinct pathway activation signatures in various breast cancer subtypes.
  • These identified subgroups may correlate with differences in tumor biological behavior and clinical treatment outcomes, warranting further investigation.
Keywords:
Breast cancer intrinsic subtypesHER2-positive breast cancerhierarchical clusteringmitogen-activated protein kinasephosphatidylinositol-3-kinasetriple-negative breast cancer

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