title: Subclassification of newly diagnosed glioblastomas through an immunohistochemical approach.
abstract: 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 for subclass assignment for GBMs is proposed. Positive staining for IDH1R132H can be used for PN subclass assignment, high EGFR expression for the CLAS subtype and a combined high expression of PTEN, VIM and/or YKL40 for the MES subclass. The application of the proposed scheme was evaluated in an independent tumor set, which resulted in similar subclass assignment rates as those observed in the training set. The IHC-based subclassification scheme proposed in this study therefore could provide very useful in future studies for stratification of individual patient samples.
authors.affiliation: Department of Pathology and Medical Biology (Division of Pathology), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Siobhan
authors.initials: S
authors.lastname: Conroy
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Frank A E
authors.initials: FA
authors.lastname: Kruyt
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Justin V
authors.initials: JV
authors.lastname: Joseph
authors.affiliation: Department of Neuroscience, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Veerakumar
authors.initials: V
authors.lastname: Balasubramaniyan
authors.affiliation: Department of Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Bhat
authors.affiliation: Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Wagemakers
authors.affiliation: Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Roelien H
authors.initials: RH
authors.lastname: Enting
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Annemiek M E
authors.initials: AM
authors.lastname: Walenkamp
authors.affiliation: Department of Pathology and Medical Biology (Division of Pathology), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005909:Glioblastoma / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors