title: Twist predicts poor outcome of patients with astrocytic glioma.
abstract: OBJECTIVE
  Epithelial-mesenchymal transition (EMT) has previously been linked to glioma invasion and progression. To determine whether EMT regulators, Twist and Zeb1, had clinical significance in astrocytic gliomas, the association of Twist and Zeb1 with clinicopathological and molecular factors was studied in 269 astrocytoma samples.
  
  
  RESULTS
  Twist and Zeb1 were widely expressed in astrocytic gliomas, but the expression of the former did not correlate with that of the latter. Stronger Twist expression levels were associated with higher WHO grades (p=0.001), whereas Zeb1 did not correlate with WHO grades. We found no association between Twist and proliferation activity (Ki67/MIB-1), p53 status, epidermal growth factor receptor (EGFR) amplification or neural cell adhesion molecule (NCAM) expression. There was no significant difference in Twist or Zeb1 expression when primary and secondary gliomas were analysed. Tumours with high Twist expression were IDH1 negative (p=0.009). High hypoxia-inducible factor-1α expression correlated significantly with positive Twist expression (p<0.001), whereas it was not associated with Zeb1 expression. Zeb1 expression did not correlate with proliferation, EGFR or IDH1. Nevertheless, we did find a correlation between high Zeb1 expression and low p53 expression levels (p=0.027). Positive NCAM expression was significantly associated with Zeb1 positivity (p=0.022). Zeb1 had no association with patient survival, whereas positive Twist expression predicted poor survival for patients in both univariate (p<0.001) and multivariable analyses (p=0.027).
  
  
  CONCLUSIONS
  EMT regulators, Twist and Zeb1, are common features of infiltrating astrocytomas, and Twist is upregulated in glioblastomas in particular. Twist may be a novel marker for poor prognosis in glioma patients.
authors.affiliation: Department of Pediatrics, Tampere University Hospital, Tampere, Finland Fimlab Laboratories Ltd, Tampere University Hospital, Tampere, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Nordfors
authors.affiliation: Fimlab Laboratories Ltd, Tampere University Hospital, Tampere, Finland Unit of Neurosurgery, Tampere University Hospital, Tampere, Finland.
authors.forename: Joonas
authors.initials: J
authors.lastname: Haapasalo
authors.affiliation: Fimlab Laboratories Ltd, Tampere University Hospital, Tampere, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Mäkelä
authors.affiliation: Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland Department of Signal Processing, Tampere University of Technology, Tampere, Finland.
authors.forename: Kirsi J
authors.initials: KJ
authors.lastname: Granberg
authors.affiliation: Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Nykter
authors.affiliation: Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Miikka
authors.initials: M
authors.lastname: Korja
authors.affiliation: Fimlab Laboratories Ltd, Tampere University Hospital, Tampere, Finland Department of Pathology, University of Tampere, Tampere, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Paavonen
authors.affiliation: Fimlab Laboratories Ltd, Tampere University Hospital, Tampere, Finland Department of Pathology, University of Tampere, Tampere, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
authors.affiliation: Department of Pathology/Forensic Medicine, Institute of Clinical Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, Kuopio, Finland.
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis*; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis; D051879:Twist-Related Protein 1 / Q000032:analysis / Q000096:biosynthesis*; D015854:Up-Regulation; D055815:Young Adult; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: BRAIN TUMOURS; IMMUNOHISTOCHEMISTRY; PAEDIATRIC PATHOLOGY