Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival

Abstract

BackgroundPatients 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. Study designTumour 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. ResultsHCMV 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). ConclusionThe 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.