Abstract

BackgroundGlioblastoma multiforme (GBM) represent the most aggressive brain tumor with a median overall survival of about 12-15 months. Over 90% of GBM tumors have recently been shown to be infected with human cytomegalovirus (HCMV). In this case-control study, we evaluated whether there was an association between the grade of HCMV infection and long-term survival (> 18 months) in GBM patients.Material and methodsBrain tumor tissue sections from consecutive GBMs patients who survived more than 18 months (n = 40), and an equal number of GBM patients, matched to date of diagnosis and surgery, operated at Karolinska University Hospital in 2000-2005 were selected. HCMV infection grade was determined by estimation of the number of HCMV positive cells (scored negative or grade 1-4) in tumor tissue specimens. Using Chi-Square test and logistic regression analysis, we analyzed whether there was an association between long-term survival and HCMV low-grade infection or other clinical parameters known to be associated with prolonged survival of GBM patients; age under 50 years, radical surgery or low recursive partition analysis (RPA) subclass.ResultsHCMV infection was detected in tumor samples from 79 of 80 patients (99%). Among patients surviving > 18 months, HCMV infection grade 1 in the GBM tumor was predominant. A low grade HCMV infection was found in 19 patients, of these 16 survived > 18 months. Thus, 16 of 40 (40%) GBM patients who lived > 18 months had low-grade HCMV infection while only 3 of 40 (8%) GBM patients who lived < 18 months did (p .0006, Chi-Square test). Multiple logistic regression analyses yielded an odds ratio estimate of 6.604 with 95% confidence interval (1.36-32.1) (p .019) for low grade HCMV after adjustment for RPA class III and IV, radical surgery, age and gamma knife treatment.ConclusionIn conclusion, we found that low-grade HCMV infection was strongly associated with long-term survival in GBM patients.

Highlights

  • Glioblastoma multiforme grade IV (GBM) is the most aggressive and common brain tumor in humans

  • A low grade human cytomegalovirus (HCMV) infection was found in 19 patients, of these 16 survived > 18 months

  • In conclusion, we found that low-grade HCMV infection was strongly associated with long-term survival in GBM patients

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Summary

Introduction

Glioblastoma multiforme grade IV (GBM) is the most aggressive and common brain tumor in humans. Viral reactivation can occur when latently infected monocytes undergo differentiation to macrophages or dendritic cells, which involves stimulation with inflammatory cytokines [9,10]. It is possible that the inflammatory environment in the glioblastoma tumor triggers reactivation of latent HCMV. Glioblastoma multiforme (GBM) represent the most aggressive brain tumor with a median overall survival of about 12-15 months. Over 90% of GBM tumors have recently been shown to be infected with human cytomegalovirus (HCMV). In this case-control study, we evaluated whether there was an association between the grade of HCMV infection and long-term survival (> 18 months) in GBM patients

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