title: The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: pathological consideration of their potential roles.
abstract: 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)-1α 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-1α 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.
authors.affiliation: Department of Neurosurgery, Osaka Medical College, Takatsuki, Japan.
authors.forename: Naosuke
authors.initials: N
authors.lastname: Nonoguchi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Miyatake
authors.forename: Motoi
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Motomasa
authors.initials: M
authors.lastname: Furuse
authors.forename: Ryo
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawabata
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kuroiwa
authors.forename: Motomu
authors.initials: M
authors.lastname: Tsuji
authors.forename: Manabu
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011379:Prognosis; D011832:Radiation Injuries / Q000209:etiology* / Q000601:surgery; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A