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Expression of vascular Notch ligands Delta-like 4 and Jagged-1 in glioblastoma
- Source :
- Histopathology; Vol 60, Histopathology
- Publication Year :
- 2012
-
Abstract
- Aims: The coordinated expression of the Notch ligands Delta-like 4 (Dll4) and Jagged (Jag)1 is believed to define appropriate endothelial sensitivity to vascular endothelial growth factor (VEGF). Preclinical data suggest that Dll4-Notch signalling may confer resistance to anti-VEGF therapy with bevacizumab, and Jag1 may antagonize Dll4-Notch. The aims of this study were to characterize the expression of Dll4 and Jag1 in primary glioblastomas. Methods and results: Immunohistochemistry was performed on 40 glioblastomas and normal brain using validated antibodies against Dll4 and Jag1. In-situ hybridization for Dll4 was performed on serial sections and compared with protein expression. Dll4 expression was localized to the cytoplasm and membrane of endothelial cells in all glioblastomas; it was weak or absent in normal brain. Jag1 expression was observed in the cytoplasm and membrane of glomeruloid and non-glomeruloid endothelial cells from 76% and 67% of glioblastomas, respectively. However, endothelial Jag1 expression was less intense and less prevalent than Dll4. There was no association between Dll4 and Jag1 expression. Conclusions: In summary, Dll4 and Jag1 are expressed in glioblastoma vasculature. These data may define subsets of glioblastoma that might be sensitive (Dll4 +/Jag1 +) or resistant (Dll4 +/Jag1 -) to bevacizumab. Our data also suggest that anti-Dll4 therapy should be evaluated experimentally in glioblastoma. © 2012 Blackwell Publishing Limited.
- Subjects :
- cardiovascular system
Subjects
Details
- Language :
- English
- ISSN :
- 13652559 and 03090167
- Volume :
- 60
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Histopathology
- Accession number :
- edsair.dedup.wf.001..ccef4d2dbe349368d2a8f2c98771e7c9