title: Histopathological investigation of glioblastomas resected under bevacizumab treatment.
abstract: To date, no clinical observations have been reported for histopathological changes in human gliomas under antiangiogenic treatment.We collected six glioblastomas resected under bevacizumab treatment. Histopathological investigation was performed by hematoxilyn-eosin staining and immunohistochemistry for CD34, VEGF, VEGFR1/2, HIF-1α, CA9, and nestin as compared to eleven control glioblastomas to assess the differences in histological features, microvessel density, expression of VEGF and its receptors, tumor oxygenation, and status of glioma stem-like cells.In the six tumors resected under bevacizumab, microvascular proliferation was absent, and microvessel density had significantly decreased compared with that of the controls. The expressions of VEGF and its receptors were downregulated in two cases of partial response. HIF-1α or CA9 expression was decreased in five of the six tumors, whereas the decreased expression of these markers was noted in only one of the 11 control glioblastomas. The expression of nestin significantly decreased in the six tumors compared with that of the controls, with the remaining nestin-positive cells being relatively concentrated around vessels.We provide the first clinicopathological evidence that antiangiogenic therapy induces the apparent normalization of vascular structure, decrease of microvessel density, and improvement of tumor oxygenation in glioblastomas. These in situ observations will help to optimize therapy.
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tamura
authors.affiliation: Department of Neurosurgery, Jikei University Kashiwa Hospital, Kashiwashita, Kashiwa-shi, Chiba, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Neurosurgery, Kagawa University Hospital, Ikedo, Mituki-cho, Kita-gun, Kagawa, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyake
authors.affiliation: Department of Neurosurgery, Japan Red Cross Medical Center, Hiroo, Shibuya-ku, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tabei
authors.affiliation: Division of Diagnostic Pathology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ohara
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Oltea
authors.initials: O
authors.lastname: Sampetrean
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Kono
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Mizutani
authors.affiliation: Department of Neurosurgery, Jikei University Kashiwa Hospital, Kashiwashita, Kashiwa-shi, Chiba, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Neurosurgery, Jikei University Hospital, Nishishinbashi, Minato-ku, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Murayama
authors.affiliation: Department of Neurosurgery, Kagawa University Hospital, Ikedo, Mituki-cho, Kita-gun, Kagawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tamiya
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008297:Male; D055806:Microvessels / Q000187:drug effects; D008875:Middle Aged
chemical_list: D020533:Angiogenesis Inhibitors; D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab
keywords: bevacizumab; glioma stem cell; hypoxia; neoadjuvant; vascular normalization