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

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

Clin Cancer Res. 2016 Dec 29;:

Authors: Holdhoff M, Guner G, Rodriguez FJ, Hicks JL, Zheng Q, Forman MS, Ye X, Grossman SA, Meeker AK, Heaphy CM, Eberhart CG, De Marzo AM, Arav-Boger R

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.

PMID: 28034905 [PubMed - as supplied by publisher]

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