gms | German Medical Science

Objective: Cytomegalovirus (CMV) has been linked to glioblastoma for over a decade,while its oncomodulatory role is poorly understood.Despite ample evidence, CMV remains notoriously hard to detect in glioblastoma samples, rendering the field an ongoing a matter of debate. Here we found evidence that serostatus, staining and mRNA expression concur and correlate with the clinical outcome in patients with glioblastoma.

Methods: 25 patients with glioblastoma (16 male, 9 females; mean age 67.2+-12.27 years) and 10 controls (5 male, 5 females; mean age 60.3+-11.63 years) were included in our study. All patients were treatment as inpatients at our department and received adjuvant therapy in our outpatient clinic. All patients were followed up every 3 months until time of death. Polymerase chain reaction was used to detect CMV (PCR). Anti-CMV IgM and IgG were measured using Enzyme linked immunosorbent assays (ELISA). Tumor samples were stained via immunofluorescence using an anti-CMV polyclonal- and anti-pp65 monoclonal antibody. CMV immediate early gene (IE1) and envelope glycoprotein B (gB) mRNA expression in tumor specimen was analyzed using RT-PCR.

Results: Anti-CMV IgG were detected in 17 (68%) patients and 6 (60%) controls. Anti-CMV IgM or viral DNA were not detected. Thus, there was no higher prevalence of seropositivity in patients with glioblastoma compared to controls. CMV IgG antibody levels ranged from levels 1.1 to >250 U (131.1+-84.92 U). CMV antigens were detect in tumor specimen of all seropositive patients and were absent from those who were seronegative. Using RT-PCR, IE1 and gB were only detected in tumors from seropositive patients while it was not detectable in total RNA from normal cerebral cortex of healthy individuals. In oour cohort, mean progression free survival (PFS) was significantly shorter in seropositive glioblastoma patients (187.8+-125.7) compared to CMV naïve patients (361.9+-212.6 days; p=0.037). Higher Serum IgG levels correlated with longer PFS (r=0.6; p=0.021) and weaker fluorescence staining. Mean overall survival was shorter in patients with past CMV infection (322 days) compared to CMV negative patients (487.5 days).

Conclusion: Our findings ad proof that CMV latency does lead to tumoritropic infection and strengthen the importance of an oncomodulatory role of CMV in glioblastoma. Seropositivity does correlate with shortened PFS and OS.