gms | German Medical Science

62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

07. - 11. Mai 2011, Hamburg

Comparative epigenetic analysis of the malignant progression of pleomorphic xanthoastrocytoma

Meeting Abstract

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  • R. Martínez - Klinik für Neurochirurgie der Universität Göttingen
  • V. Rohde - Klinik für Neurochirurgie der Universität Göttingen
  • S. Ropero - Department of Biochemistry and Molecular Biology, University of Madrid, Spain
  • M. Esteller - Cancer Epigenetics and Biology Program, IDIBELL, Barcelona, Spain

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocP 029

DOI: 10.3205/11dgnc250, URN: urn:nbn:de:0183-11dgnc2507

Veröffentlicht: 28. April 2011

© 2011 Martínez et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Pleomorphic xanthoastrocytoma (PXA) is a rare WHO grade II tumor accounting for less than 1% of all astrocytomas. The biological behavior of PXA is benign with a 10-year survival rate of 70%. Malignant transformation of PXA is extremely unusual. We report the exceptional case of a patient harboring a WHO grade II right parietal PXA. 12 months after total resection, a local relapse occurred. Histologically, the recurrent tumor showed anaplastic features.

Methods: Both tumor specimens were assessed by histological, immunohistochemical and molecular analyses. After DNA extraction, methylation-specific polymerase chain reaction (MSP) was applied for pro-apoptotic genes (CASP8, CASP3, CASP9, DcR1, DR4, DR5, TMS1), tumor suppressor genes (RASSF1A, BLU), cell adhesion regulating genes (CDH1, CDH13), cell cycle regulator genes (CHFR, p14ARF, p16INK) and DNA repair genes (MGMT, hMLH1). Bisulfite sequencing was performed in selected cases to confirm MSP data.

Results: Both tumors were similar regarding immunopositivity against GFAP, S100, vimentin and EMA. The proliferation activity (assessed by MIB1) was higher in the malignant specimen (20% vs. 10%). p53 immunopositivity was more frequently observed in the anaplastic sample (20% vs. 10%). RASFF1A, TMS1 and MGMT were hypermethylated in both tumors, whereas BLU and DR4 showed a new methylation in the anaplastic tumor not previously observed in the benign specimen.

Conclusions: The anaplastic features of the 2nd PXA were underscored by higher tumor proliferation activity and p53 accumulation. Anaplastic transformation of PXA was accompanied by epigenetic inactivation of the tumor suppressor gene BLU and the pro-apoptotic gene DR4. Our data further suggest that methylation-mediated inactivation of RASFF1A, TMS1 and MGMT may be early events in the pathogenesis of PXA.