title: Prevalence and clinicopathologic characteristics of the molecular subtypes in malignant glioma: a multi-institutional analysis of 941 cases.
abstract: BACKGROUND
  Glioblastoma can be classified into four distinct molecular subtypes (Proneural, Neural, Classical and Mesenchymal), based on gene expression profiling. This study aimed to investigate the prevalence, clinicopathologic features and overall survival (OS) of the four molecular subtypes among all malignant gliomas.
  
  
  METHODS
  A total of 941 gene expression arrays with clinical data were obtained from the Rembrandt, GSE16011 and CGGA datasets. Molecular subtypes were predicted with a prediction analysis of microarray.
  
  
  RESULTS
  Among 941 malignant gliomas, 32.73% were Proneural, 15.09% Neural, 19.77% Classical and 32.41% Mesenchymal. The Proneural and Neural subtypes occurred largely in low-grade gliomas, while the Classical and Mesenchymal subtypes were more frequent in high-grade gliomas. A survival analysis showed that the Proneural subtype displayed a good prognosis, Neural had an intermediate correlation with overall survival, Mesenchymal had a worse prognosis than Neural, and Classical had the worst clinical outcome. Furthermore, oligodendrocytomas were preferentially assigned to the Proneural subtype, while the Mesenchymal subtype included a higher percentage of astrocytomas, compared with oligodendrocytomas. Additionally, nearly all classical gliomas harbored EGFR amplifications. Classical anaplastic gliomas have similar clinical outcomes as their glioblastoma counterparts and should be treated more aggressively.
  
  
  CONCLUSIONS
  Molecular subtypes exist stably in all histological malignant gliomas subtypes. This could be an important improvement to histological diagnoses for both prognosis evaluations and clinical outcome predictions.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Kaiming
authors.initials: K
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yinyi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000145:classification* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000145:classification* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D060787:Neoplasm Grading; D015995:Prevalence; D011379:Prognosis; D012372:ROC Curve; D016019:Survival Analysis; D014944:World Health Organization
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors
references.citation: Cancer Res. 2009 Dec 1;69(23):9065-72
references.pmid: 19920198
references.citation: Mol Cancer Res. 2009 Feb;7(2):157-67
references.pmid: 19208739
references.citation: Proc Natl Acad Sci U S A. 2002 May 14;99(10):6567-72
references.pmid: 12011421
references.citation: Genes Dev. 2007 Nov 1;21(21):2683-710
references.pmid: 17974913
references.citation: Expert Rev Neurother. 2009 Apr;9(4):519-34
references.pmid: 19344303
references.citation: Neuro Oncol. 2012 Dec;14(12):1432-40
references.pmid: 23090983
references.citation: Cancer Cell. 2006 Mar;9(3):157-73
references.pmid: 16530701
references.citation: Cancer Res. 2009 Mar 1;69(5):2091-9
references.pmid: 19244127
references.citation: J Exp Clin Cancer Res. 2011 May 17;30:58
references.pmid: 21575270
references.citation: Cancer Cell. 2010 Jan 19;17(1):98-110
references.pmid: 20129251
references.citation: Cancer Lett. 2013 May 1;331(2):139-46
references.pmid: 23340179
references.citation: Glia. 1995 Nov;15(3):211-21
references.pmid: 8586458