Expression of cytomegalovirus in glioblastoma multiforme: Myth or reality?

Abstract

A role for human cytomegalovirus (HCMV) in the pathogenesis of glioblastoma multiforme (GBM) was proposed more than a decade ago and has since generated a considerable debate as a possible therapeutic target. We investigate the presence of HCMV in the specimens of patients with GBM treated in our centre. This is a retrospective cohort study to investigate the presence of HCMV by routine immunohistochemical stains and polymerase chain reaction (PCR)-based molecular analysis on formalin-fixed-paraffin-embedded tissue of all patients with GBM treated in our hospital in 2009-2013 (5 years). The evaluation of positivity by immunohistochemistry (IHC) was semi-quantitative. The molecular analysis was performed by extracting the tumour DNA from representative paraffin-embedded tissue blocks and amplified for detection by a sensitive real time PCR (RT-PCR) CMV assay. During the study period, we treated 45 patients with GBM; however, adequate pathology tissue materials were available only for 32 patients. All the pathology material was reviewed and the diagnosis was confirmed. All the cases were found to be negative for CMV expression by our IHC and RT-PCR CMV assay. Our study has shown no expression of CMV in GBM. Our results were similar to other recent reports that concluded insufficient evidence to recommend routine testing for CMV in GBM or treatment as an add-on therapy.

Detection of human cytomegalovirus in glioblastoma among Taiwanese subjects

“…In addition to the probes, denaturation, hybridization and detection could be different, and might account for the different outcomes. Similar to our results, a recent report showed no expression of HCMV in 32 GBM by IHC and RT-PCR HCMV assay [39]. …”

Cidofovir is active against human papillomavirus positive and negative head and neck and cervical tumor cells by causing DNA damage as one of its working mechanisms

“…originating form cervical or head and neck tissues), indicating that CDV may be considered a broad-spectrum anti-tumor agent. Hadaczek et al also showed that CDV inhibits glioblastoma both in vitro and in vivo , regardless of the presence of human cytomegalovirus (HCMV) [25], however a role for HCMV in the pathogenesis of glioblastoma is controversial [35]. It was previously shown that the in vitro and in vivo antiproliferative activities of CDV against nasopharyngeal carcinoma (which is driven by Epstein-Barr virus) were not due to inhibition of the viral DNA polymerase [27].…”

Human Cytomegalovirus DNA Quantification and Gene Expression in Gliomas of Different Grades

“…Most studies show a positive association between HCMV and gliomas [ 1 , 20 – 39 ]. Nevertheless, there are investigations that could not confirm the presence of the virus in the tumors and controversy in the field persists [ 19 , 40 – 47 ]. In addition, few studies investigated the correlation between expression of viral genes and proteins in gliomas with tumor malignancy [ 20 , 30 , 36 , 37 , 48 ].…”