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Absence of cytomegalovirus in glioblastoma and other high-grade gliomas by real-time PCR, immunohistochemistry and in situ hybridization.


Posted on: 12/31/2016

Clin Cancer Res. 2016 Dec 29. pii: clincanres.1490.2016. doi: 10.1158/1078-0432.CCR-16-1490. [Epub ahead of print]
Absence of cytomegalovirus in glioblastoma and other high-grade gliomas by real-time PCR, immunohistochemistry and in situ hybridization.
Holdhoff M1, Guner G2, Rodriguez FJ3, Hicks JL4, Zheng Q5, Forman MS6, Ye X7, Grossman SA7, Meeker AK8, Heaphy CM4, Eberhart CG9, De Marzo AM5, Arav-Boger R10.
 
Author information:
1Oncology, Johns Hopkins University School of Medicine mholdho1@jhmi.edu.
2Pathology, Johns Hopkins University.
3Department of Anatomic Pathology and Laboratory Medicine, Mayo Clinic.
4Pathology, Johns Hopkins University School of Medicine.
5Department of Pathology, Johns Hopkins University.
6Johns Hopkins Hospital, Microbiology Labs, Johns Hopkins Medical Institutions.
7Oncology, Johns Hopkins.
8Department of Pathology, Johns Hopkins School of Medicine.
9Pathology,Oncology, Ophthalmology, Johns Hopkins University School of Medicine.
10Pediatrics, Johns Hopkins Hospital.
 
Abstract
PURPOSE:
 
Reports of cytomegalovirus (CMV) detection in high-grade gliomas (HGG)/glioblastoma (GBM) have been conflicting. We undertook a comprehensive approach to determine presence or absence of CMV in tissue, plasma and serum of HGG patients.
EXPERIMENTAL DESIGN:
 
In a retrospective arm, 25 fresh frozen tissues from GBM patients were tested for CMV by real-time PCR. Tissue microarrays from 70 HGG patients were tested by immunohistochemistry (IHC) and 20 formalin-fixed paraffin-embedded (FFPE) GBM tissues by IHC and chromogenic in situ hybridization (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 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 3 orthogonal technologies on multiple specimens and specimen types, no evidence for CMV in GBM 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/GBM for future guidance on the necessity anti-viral and/or CMV-based therapies.
 
Copyright ©2016, American Association for Cancer Research.
PMID: 28034905 [PubMed - as supplied by publisher]

 


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