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Twist predicts poor outcome of patients with astrocytic glioma
  1. Kristiina Nordfors1,2,
  2. Joonas Haapasalo2,3,
  3. Katri Mäkelä2,
  4. Kirsi J Granberg4,5,
  5. Matti Nykter4,
  6. Miikka Korja6,7,
  7. Timo Paavonen2,8,
  8. Hannu Haapasalo2,8,
  9. Ylermi Soini9
  1. 1Department of Pediatrics, Tampere University Hospital, Tampere, Finland
  2. 2Fimlab Laboratories Ltd, Tampere University Hospital, Tampere, Finland
  3. 3Unit of Neurosurgery, Tampere University Hospital, Tampere, Finland
  4. 4Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland
  5. 5Department of Signal Processing, Tampere University of Technology, Tampere, Finland
  6. 6Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
  7. 7Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia
  8. 8Department of Pathology, University of Tampere, Tampere, Finland
  9. 9Department of Pathology/Forensic Medicine, Institute of Clinical Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, Kuopio, Finland
  1. Correspondence to Dr Kristiina Nordfors, Department of Pediatrics, Tampere University Hospital, P.O. Box 2000, Tampere 33521, Finland; kristiina.nordfors{at}gmail.com

Abstract

Aims and methods 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.

  • BRAIN TUMOURS
  • PAEDIATRIC PATHOLOGY
  • IMMUNOHISTOCHEMISTRY

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