Mar. 25, 2010 Dr. Adrian L. Harris and colleagues at the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK have discovered that high expression levels of delta-like ligand 4 (DLL4) predict poor prognosis in breast cancer.
They present these findings in the April 2010 issue of the American Journal of Pathology.
Survival of patients with breast cancer is dependent on cancer stage, aggressiveness, and genetic makeup. New diagnostic markers that predict prognosis would therefore aid in therapeutic decision-making.
DLL4, a cell-signalling molecule expressed on endothelial cells, is regulated by the therapeutic target VEGF (vascular endothelial growth factor) as well as by low oxygen levels, suggesting that it plays possible roles in new blood vessel formation and growth in tumors. To explore the role of DLL4 in breast cancer, Jubb et al examined breast adenocarcinomas, normal breast tissues, and angiosarcomas. They found that DLL4 was expressed in endothelial cells within the tumor proper of breast adenocarcinomas, but not in normal non-lactating breast tissue, and that high expression levels of DLL4 predicted poor prognosis regarding both overall and relapse-free survival. Assessing which patients express DLL4 may therefore may be used to predict patients' responsiveness to anti-VEGF therapies.
Dr. Harris and colleagues "suggest that tumor endothelial expression of Dll4 is a significant prognostic factor in early breast adenocarcinoma." They believe "these data may have clinical relevance, as preclinical models suggest that assessing which patients express Dll4 in their tumor endothelium may be critical in predicting benefit from anti-VEGF therapies."
Jubb AM, Soilleux EJ, Turley H, Steers G, Parker A, Low I, Blades J, Li J-L, Allen P, Leek R, Noguera-Troise I, Gatter KC, Thurston G, Harris AL: Expression of Vascular Notch Ligand Delta-like 4 (Dll4) and Inflammatory Markers in Breast Cancer. Am J Pathol 2010 176, 2019-2028
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