title: Low levels of Human Cytomegalovirus Infection in Glioblastoma multiforme associates with patient survival; -a case-control study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Brain 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.
  
  
  RESULTS
  HCMV 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.
  
  
  CONCLUSIONS
  In conclusion, we found that low-grade HCMV infection was strongly associated with long-term survival in GBM patients.
authors.affiliation: Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
authors.forename: Afsar
authors.initials: A
authors.lastname: Rahbar
authors.affiliation: Department of Neurology , Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Stragliotto
authors.affiliation: Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Abiel
authors.initials: A
authors.lastname: Orrego
authors.affiliation: Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.|Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Inti
authors.initials: I
authors.lastname: Peredo
authors.affiliation: Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
authors.forename: Chato
authors.initials: C
authors.lastname: Taher
authors.affiliation: Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Willems
authors.affiliation: Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Söderberg-Naucler