P01.14 * PRESENCE OF A STEM CELL-LIKE CELL SUBPOPULATION IS ASSOCIATED WITH ENHANCED SURVIVAL OF GLIOBLASTOMA PATIENTS

Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumours characterised by a dismal prognosis and limited treatment response. The current standard of care for GBM patients includes after tumour resection, radiotherapy (RT) followed by concomitant and adjuvant chemotherapy with the alkylating agent temozolomide (TMZ). Even at this maximal therapy the prognosis of GBM patients remains poor with a median survival of 15 months. It is believed that a subpopulation of glioma stem cells (GSC) is responsible for maintaining a tumour after therapy thus causing recurrence after gross total resection. Accordingly aim of this study was to correlate the presence of GSCs with the predictive and prognostic glioblastoma biomarkers MGMT promoter methylation and TERT promoter mutation, respectively. In addition we investigated the prognostic quality of a GSC subpopulation on patient overall survival. For that purpose 33 primary and recurrent GBM patients operated at the Medical University of Vienna since September 2009 were included in this project. Every resected tumour sample was cultured in parallel as adherent monolayer under standard and as spheroids under GSC culture conditions. Fourteen out of 33 GBM tissue specimens (42%) developed into adherent and neurosphere cultures (termed GCSpos), while the remaining 19 (58%) could solely grow as adherent monolayer (termed GSCneg). The mean age of GSCpos patients was significantly lower as compared to the GSCneg subgroup (53 versus 63 years). The GSCpos cohort was characterized by significantly enhanced occurrence of MGMT promoter methylation and TERT promoter mutation. Surprisingly, GCSpos compared to GCSneg patients showed a significant prolonged overall survival (p = 0.0045). Summarizing our data suggest that GBM tumours harbouring GSC characteristics might be more likely to respond to standard therapy with TMZ due to the favourable MGMT promoter methylation status explaining, beside lower patient age, enhanced survival.