title: Assessment of vascularity in glioblastoma and its implications on patient outcomes.
abstract: There is little data on why glioblastomas (GBM) hemorrhage and how it may affect patient outcomes. The aim of this study was to investigate the mechanisms of hemorrhage in glioblastoma by examining molecular and genetic features by immunohistochemistry (IHC) and mRNA expression profiles in association with imaging and clinical outcomes. An observational retrospective cohort analysis was performed on 43 FFPE GBM tissue samples. MR images were assessed for the presence of hemorrhage and extent of resection. Specimens were examined for CD34 and CD105 expression using IHC. Tumor mRNA expression profiles were analyzed for 92 genes related to angiogenesis and vascularity. Forty-three specimens were analyzed, and 20 showed signs of hemorrhage, 23 did not. The average OS for patients with GBM with hemorrhage was 19.12 months (95% CI 10.39-27.84), versus 13.85 months (95% CI 8.85-18.85) in those without hemorrhage (p > 0.05). Tumors that hemorrhaged had higher IHC staining for CD34 and CD105. mRNA expression analysis revealed tumor hemorrhage was associated with increased expression of HIF1α and MDK, and decreased expression of F3. Hemorrhage in GBM was not associated with worsened OS. Increased expression of angiogenic factors and increased CD34 and CD105 IHC staining in tumors with hemorrhage suggests that increased hypoxia-induced angiogenesis and vessel density may play a role in glioblastoma hemorrhage. Characterizing tumors that are prone to hemorrhage and mechanisms behind the development of these hemorrhages may provide insights that can lead to the development of targeted, individualized therapies for glioblastoma.
authors.affiliation: Division of Neurosurgery, University of Nebraska Medical Center, 982035 Nebraska Medical Center, Omaha, NE, 68198-2035, USA.
authors.forename: Ben G
authors.initials: BG
authors.lastname: McGahan
authors.affiliation: Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, USA.
authors.forename: Beth K
authors.initials: BK
authors.lastname: Neilsen
authors.affiliation: Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kelly
authors.affiliation: Department of Pathology, University of Nebraska Medical Center, Omaha, USA.
authors.forename: Rodney D
authors.initials: RD
authors.lastname: McComb
authors.affiliation: Geisinger Medical Laboratories, Geisinger Medical Center, Danville, PA, USA.
authors.forename: S A Jaffar
authors.initials: SA
authors.lastname: Kazmi
authors.affiliation: Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Matt L
authors.initials: ML
authors.lastname: White
authors.affiliation: Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Neurosurgery, University of Nebraska Medical Center, 982035 Nebraska Medical Center, Omaha, NE, 68198-2035, USA. maizenberg@unmc.edu.
authors.forename: Michele R
authors.identifier: 0000-0001-6689-8907
authors.initials: MR
authors.lastname: Aizenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D001932:Brain Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000378:metabolism*; D000071063:Endoglin / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000098:blood supply* / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D018952:Antigens, CD34; C064206:ENG protein, human; D000071063:Endoglin; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger
keywords: Gene analysis; Glioblastoma; HIF1α; Hemorrhage; Vascularity