Journal of Neuro-Oncology

, Volume 104, Issue 1, pp 113–118 | Cite as

Retrospective protein expression and epigenetic inactivation studies of CDH1 in patients affected by low-grade glioma

  • Pietro Ivo D’Urso
  • Oscar Fernando D’Urso
  • Carlo Storelli
  • Giuseppe Catapano
  • Cosimo Damiano Gianfreda
  • Antonio Montinaro
  • Antonella Muscella
  • Santo Marsigliante
Laboratory Investigation - Human/Animal Tissue
First Online:
Received:
Accepted:

Abstract

Aberrant methylation of CpG islands in the promoter regions of tumour cells results in loss of gene function. In addition to genetic lesions, changes in the methylation profile of the promoters may be considered a factor for tumour-specific aberrant expression of the genes.We investigated the methylation status of E-cadherin gene (CDH1) promoter in low-grade glioma and correlated it with clinical outcome. Eighty-four cases of low-grade glioma (43 diffuse astrocytomas, 27 oligodendrogliomas and 14 oligoastrocytomas) with assessable paraffin-embedded tumour blocks and normal brain tissue, derived from non-cancerous tissue adjacent to tumour and commercially normal brain tissue, were collected, from which we determined CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction (MSP) and immunohistochemistry, respectively. CDH1 promoter was found hypermethylated in 54 out of 84 low grade gliomas (64%) compared with 84 normal brain tissue. CDH1 hypermethylation was found in 65% astrocytomas, 66% oligodendrogliomas and 57% oligoastrocytomas. A significant correlation between hypermethylation status, patient survival and progression-free survival was found (P = 0.04). Survival and progression-free survival were lower in patients with hypermethylated CDH1 promoter. We found that 15 astrocytomas, 9 oligodendrogliomas and 6 oligoastrocytomas were immunoreactive for E-cadherin. The incidence of loss of immunoreactivity for E-cadherin decreased significantly with age, overall survival and progression-free survival (P = 0.001, Kaplan–Meier test). We have demonstrated that CDH1 promoter hypermethylation significantly associated with down-regulated E-cadherin expression and overall survival of patients. This may have a bearing on the prognosis of low-grade glioma.

Keywords

Low-grade glioma E-cadherin CDH1 methylation Tumour suppressor gene 
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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Pietro Ivo D’Urso
    • 1
  • Oscar Fernando D’Urso
    • 2
  • Carlo Storelli
    • 2
  • Giuseppe Catapano
    • 1
  • Cosimo Damiano Gianfreda
    • 3
  • Antonio Montinaro
    • 3
  • Antonella Muscella
    • 2
  • Santo Marsigliante
    • 2
  1. 1.Department of Neurological Sciences, U.O. Neurosurgery“G. Rummo” HospitalBeneventoItaly
  2. 2.Department of Biological and Environmental Sciences and Technologies (DISTEBA)LecceItaly
  3. 3.Neurosurgery Operative UnitV. Fazzi HospitalLecce

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