title: Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival.
abstract: BACKGROUND
  Patients with glioblastoma multiforme (GBM) generally live 12-15 months after diagnosis, despite maximal surgical resection, adjuvant radiotherapy, and chemotherapy. HCMV has been detected in 90-100% of GBMs. We recently found that low grade HCMV infection in GBM tumours was highly associated with survival over 18 months (case-control study). Here, we sought to determine whether low-grade HCMV infection in GBMs is associated with prolonged survival in a consecutive patient cohort, analysed retrospectively.
  
  
  METHODS
  Tumour samples from 75 consecutive GBM patients treated surgically at Karolinska University Hospital in 2004-2005 were examined by immunohistochemistry (IHC) and in situ hybridization for HCMV proteins and DNA, respectively. Tumours were graded 1-4, depending on the percentage of positive cells by IHC. Low-grade HCMV was defined as grade 1 (< 25% of HCMV infected tumour cells). Time to tumour progression (TTP) and survival data were analysed with Cox regression and Kaplan-Meier models.
  
  
  RESULTS
  HCMV infection was detected in 74 of 75 tumours (99%). In patients with low-grade HCMV infection, median survival was 20 months longer than in patients with high-grade infections (P = 0.036, HR: 2.2), and TTP was 8 months longer (P = 0.1, HR: 1.8). Two-year survival was much higher in patients with low-grade HCMV infection (63.6% vs. 17.2%, P = 0.003).
  
  
  CONCLUSIONS
  The longer survival in patients whose tumours had low-grade HCMV infection suggests that the level of HCMV infection in GBMs has a prognostic value and that HCMV may contribute to the pathogenesis of GBM.
authors: Department of Medicine Solna, Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors: Afsar
authors: A
authors: Rahbar
authors: Abiel
authors: A
authors: Orrego
authors: Inti
authors: I
authors: Peredo
authors: Mensur
authors: M
authors: Dzabic
authors: Nina
authors: N
authors: Wolmer-Solberg
authors: Klas
authors: K
authors: Strååt
authors: Giuseppe
authors: G
authors: Stragliotto
authors: Cecilia
authors: C
authors: Söderberg-Nauclér
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis / Q000821:virology*; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000150:complications*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis