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Published on: January 12, 2020

Expression of vascular notch ligand delta-like 4 and inflammatory markers in breast cancer

Adrian M Jubb1, Elizabeth J Soilleux, Helen Turley

  • 1Nuffield Department of Clinical Laboratory Sciences,Weatherall Institute ofMolecular Medicine, University of Oxford, Oxford, UK.

The American Journal of Pathology
|February 20, 2010
PubMed

Insights

Delta-like ligand 4 (Dll4) is expressed in breast cancer endothelium. High Dll4 expression indicates a poorer prognosis, suggesting it as a potential therapeutic target for breast cancer.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Delta-like ligand 4 (Dll4) is a Notch ligand primarily found in endothelial cells.
  • Dll4 inhibition shows promise in overcoming resistance to anti-VEGF therapy in preclinical models.
  • Its role and prognostic significance in breast cancer remain to be fully elucidated.

Purpose of the Study:

  • To characterize Dll4 expression in various breast tissue types.
  • To investigate the association between Dll4 and inflammatory markers in breast cancer.
  • To assess the prognostic value of Dll4 in breast cancer patients.

Main Methods:

  • Immunohistochemistry was used to analyze Dll4 expression in 296 breast adenocarcinomas, 38 ductal carcinoma in situ, 10 normal breast tissues, and 16 angiosarcomas.
  • Validated antibodies were employed for Dll4, CD68, CD14, DC-SIGN, CD123, neutrophil elastase, CD31, and carbonic anhydrase 9.
  • Statistical analyses, including univariate and multivariate, were performed to correlate Dll4 expression with survival outcomes and inflammatory markers.

Main Results:

  • Dll4 was selectively expressed by intratumoral endothelial cells in most breast adenocarcinomas (73-100%) and lactating breast tissues, but not in normal non-lactating breast tissue.
  • High endothelial Dll4 expression emerged as a significant adverse prognostic factor for both overall survival (P=0.002) and relapse-free survival (P=0.01) in univariate analyses.
  • In multivariate analyses, high Dll4 expression remained a significant predictor of poorer overall survival (P=0.03) and relapse-free survival (P=0.04).
  • CD68 and DC-SIGN were significant univariate prognostic factors for overall survival, but not in multivariate analysis.

Conclusions:

  • Dll4 is expressed by the endothelium associated with breast cancer cells.
  • Endothelial Dll4 expression is a significant independent prognostic factor in breast cancer.
  • These findings highlight Dll4 as a potential therapeutic target in breast cancer treatment.

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