Journal
JOURNAL OF NEURO-ONCOLOGY
Volume 105, Issue 2, Pages 423-431Publisher
SPRINGER
DOI: 10.1007/s11060-011-0610-9
Keywords
Angiogenesis; Bevacizumab; Boron neutron capture therapy; Hypoxia-inducible factor-1 alpha; Radiation necrosis; Vascular endothelial growth factor
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Funding
- Japanese Ministry of Education, Culture, Sports, Science, and Technology [16390422, 19390385]
- Takeda Science Foundation for Osaka Medical College
- OMC Science Frontier Program for the Promotion of Research in Osaka Medical College
- Grants-in-Aid for Scientific Research [19390385, 16390422, 23390355, 23659596] Funding Source: KAKEN
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The cell type and localization of vascular endothelial growth factor (VEGF)-producing cells in human radiation necrosis (RN) are investigated from a histopathological and immunohistochemical standpoint using clinical specimens. Eighteen surgical specimens of symptomatic RN in the brain were retrospectively reviewed. These cases included different original histological tumor types and were treated with different radiation modalities. Histological analyses were performed using hematoxylin and eosin (H&E) staining, and anti-VEGF and anti-hypoxia-inducible factor (HIF)-1 alpha immunohistochemistry. H&E staining showed marked angiogenesis and reactive astrocytosis at the perinecrotic area. The most prominent vasculature in this area was identified as telangiectasis. Immunohistochemistry indicated that HIF-1 alpha was expressed predominantly in the perinecrotic area and that a large majority of VEGF-expressing cells were reactive astrocytes intensively distributed in this area. VEGF produced by the reactive astrocytes localized mainly in the perinecrotic area might be a major cause of both angiogenesis and the subsequent perilesional edema typically found in RN of the brain. The benefits of anti-VEGF antibody (bevacizumab) treatment in RN may be that VEGF secretion from the perinecrotic tissue is inhibited and that surgery would remove this tissue; both of these benefits result in effective reduction of edema associated with RN.
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