title: Sox11 expression in astrocytic gliomas: correlation with nestin/c-Met/IDH1-R132H expression phenotypes, p-Stat-3 and survival.
abstract: BACKGROUND
  Sox11 is a transcription factor expressed in foetal and neoplastic brain tissue, including gliomas. It has been shown to suppress the tumourigenicity of glioma stem cells in vivo, thereby being hypothesised to function as a tumour suppressor.
  
  
  METHODS
  We investigated the expression of Sox11 in 132 diffuse astrocytomas in relation to the regulator cell marker nestin, c-Met and IDH1-R132H, which have shown to be differentially expressed among the molecular subgroups of malignant gliomas, as well as to an inducer of astrocytic differentiation, that is, signal transducer and activator of transcription (p-STAT-3), clinicopathological features and survival.
  
  
  RESULTS
  Sox11 immunoreactivity was identified in all tumours irrespective of grade, but being correlated with p-STAT-3. Three out of seven cases showed partial Sox11 promoter methylation. In >50% of our cases neoplastic cells coexpressed Sox11 and nestin, a finding further confirmed in primary glioblastoma cell cultures. Furthermore, nestin, c-Met and IDH1-R132H expression differed among grade categories. Cluster analysis identified four groups of patients according to c-Met, nestin and IDH1-R132H expression. The c-Met/nestin high-expressor group displayed a higher Sox11 expression. Sox11 expression was an indicator of favourable prognosis in glioblastomas, which remained in multivariate analysis and validated in an independent set of 72 cases. The c-Met/nestin high-expressor group was marginally with shorter survival in univariate analysis.
  
  
  CONCLUSIONS
  We highlight the importance of Sox11 expression as a favourable prognosticator in glioblastomas. c-Met/nestin/IDH1-R132H expression phenotypes recapitulate the molecular subgroups of malignant glioma.
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, 115 27, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: G
authors.initials: G
authors.lastname: Levidou
authors.forename: E A
authors.initials: EA
authors.lastname: El-Habr
authors.forename: C
authors.initials: C
authors.lastname: Adamopoulos
authors.forename: P
authors.initials: P
authors.lastname: Fragkou
authors.forename: E
authors.initials: E
authors.lastname: Boviatsis
authors.forename: M S
authors.initials: MS
authors.lastname: Themistocleous
authors.forename: K
authors.initials: K
authors.lastname: Petraki
authors.forename: G
authors.initials: G
authors.lastname: Vrettakos
authors.forename: M
authors.initials: M
authors.lastname: Sakalidou
authors.forename: V
authors.initials: V
authors.lastname: Samaras
authors.forename: A
authors.initials: A
authors.lastname: Zisakis
authors.forename: A
authors.initials: A
authors.lastname: Saetta
authors.forename: I
authors.initials: I
authors.lastname: Chatziandreou
authors.forename: E
authors.initials: E
authors.lastname: Patsouris
authors.forename: C
authors.initials: C
authors.lastname: Piperi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006639:Histidine / Q000235:genetics; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D064231:Nestin; D010641:Phenotype; D010766:Phosphorylation; D011379:Prognosis; D011494:Protein Kinases / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D006639:Histidine; D001120:Arginine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D011494:Protein Kinases; D019859:Proto-Oncogene Proteins c-met