Prognostic Subcellular Notch2, Notch3 and Jagged1 Localization Patterns in Early Triple-negative Breast Cancer

Anticancer Res. 2017 May;37(5):2323-2334. doi: 10.21873/anticanres.11570.

Abstract

Background: The Notch pathway has been implicated in triple-negative breast cancer (TNBC). Herein, we studied the subcellular localization of the less investigated Notch2 and Notch3 and that of the Jagged1 (Jag1) ligand in patients with operable TNBC.

Patients and methods: We applied immunohistochemistry for Notch2, Notch3 and Jag1 in 333 tumors from TNBC patients treated with adjuvant anthracycline-based chemotherapy. We evaluated cytoplasmic (c), membranous (m) and nuclear (n) protein localization.

Results: c-Notch2 (35% positive tumors), c-Notch3 (63%), c-Jag1 (43%), m-Notch3 (23%) and n-Jag1 (17%) were analyzed individually and by using hierarchical clustering for prognostic evaluation. Upon multivariate analysis, compared to high m-Notch3 in the absence of n-Jag1 (cluster 4), all other marker combinations (clusters 1, 2, 3) conferred significantly higher risk for relapse (p<0.05).

Conclusion: Specific Notch3 and Jag1 subcellular localization patterns may provide clues for the behavior of the tumors and potentially for Jag1 targeting in TNBC patients.

Keywords: Jagged1; Notch2; Notch3; prognosis; triple-negative breast cancer.

MeSH terms

  • Anthracyclines / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Female
  • Humans
  • Jagged-1 Protein / metabolism*
  • Middle Aged
  • Prognosis
  • Receptor, Notch2 / metabolism*
  • Receptor, Notch3 / metabolism*
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / metabolism*

Substances

  • Anthracyclines
  • Antineoplastic Agents
  • JAG1 protein, human
  • Jagged-1 Protein
  • NOTCH2 protein, human
  • NOTCH3 protein, human
  • Receptor, Notch2
  • Receptor, Notch3