title: Absence of Cytomegalovirus in Glioblastoma and Other High-grade Gliomas by Real-time PCR, Immunohistochemistry, andIn SituHybridization.
abstract: Purpose:Reports of cytomegalovirus (CMV) detection in high-grade gliomas (HGG)/glioblastoma have been conflicting. We undertook a comprehensive approach to determine the presence or absence of CMV in tissue, plasma, and serum of HGG patients.Experimental Design:In a retrospective arm, 25 fresh frozen tissues from glioblastoma patients were tested for CMV by real-time PCR. Tissue microarrays from 70 HGG patients were tested by IHC and 20 formalin-fixed paraffin-embedded (FFPE) glioblastoma tissues by IHC and chromogenicin situhybridization (CISH), targeting CMV-encoded IE1/2 and pp65. In a prospective arm, 18 patients with newly diagnosed HGG provided tissue and blood samples.Results:All retrospectively collected tissues were negative for CMV by all methods. In the prospective cohort, 18 patients with newly diagnosed HGG provided blood samples at the time of diagnosis and during follow-up. Of 38 plasma specimens, CMV DNA was detected in 3 of 18 samples at baseline and 1 of 20 follow-up samples. Serum CMV IgG was positive in 8 of 15 (53%) of patients. Among the FFPE samples tested in the prospective arm, all were negative for CMV by IHC, CISH, and PCR.Conclusions:Utilizing 6 highly sensitive assays with three orthogonal technologies on multiple specimens and specimen types, no evidence for CMV in glioblastoma tissues was found. Our findings call for multicenter blinded analyses of samples collected from different geographical areas with agreed upon study designs and determination of causality or lack thereof of CMV in HGG/glioblastoma for future guidance on the necessary antiviral and/or CMV-based therapies.Clin Cancer Res; 23(12); 3150-7. ©2016 AACR.
authors.affiliation: Brain Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland. mholdho1@jhmi.edu boger@jhmi.edu.|Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Holdhoff
authors.affiliation: Department of Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gunes
authors.initials: G
authors.lastname: Guner
authors.affiliation: Brain Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Department of Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Fausto J
authors.initials: FJ
authors.lastname: Rodriguez
authors.affiliation: Department of Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hicks
authors.affiliation: Department of Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Forman
authors.affiliation: Brain Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Department of Neurosurgery, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Xiaobu
authors.initials: X
authors.lastname: Ye
authors.affiliation: Brain Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Grossman
authors.affiliation: Department of Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.affiliation: Department of Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Heaphy
authors.affiliation: Brain Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Department of Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland. mholdho1@jhmi.edu boger@jhmi.edu.
authors.forename: Ravit
authors.initials: R
authors.lastname: Arav-Boger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000302:isolation & purification* / Q000472:pathogenicity; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D004279:DNA, Viral