RESEARCH ARTICLE Subclassification of Newly Diagnosed Glioblastomas through an Immunohistochemical Approach

Molecular signatures in Glioblastoma (GBM) have been described that correlate with clinical outcome and response to therapy. The Proneural (PN) and Mesenchymal (MES) signatures have been identified most consistently, but others including Classical (CLAS) have also been reported. The molecular signatures have been detected by array techniques at RNA and DNA level, but these methods are costly and cannot take into account individual contributions of different cells within a tumor. Therefore, the aim of this study was to investigate whether subclasses of newly diagnosed GBMs could be assessed and assigned by application of standard pathology laboratory procedures. 123 newly diagnosed GBMs were analyzed for the tumor cell expression of 23 pre-identified proteins and EGFR amplification, together allowing for the subclassification of 65 % of the tumors. Immunohistochemistry (IHC)-based profiling was found to be analogous to transcription-based profiling using a 9-gene transcriptional signature for PN and MES subclasses. Based on these data a novel, minimal IHC-based scheme fo