gms | German Medical Science

60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit den Benelux-Ländern und Bulgarien

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

24. - 27.05.2009, Münster

Expression of carbonic anhydrase IX correlates with tumor-cyst formation in craniopharyngiomas

Meeting Abstract

  • M. Proescholdt - Klinik für Neurochirurgie, Universitätsklinikum Regensburg
  • C. Mayer - Klinik für Neurochirurgie, Universitätsklinikum Regensburg
  • E.M. Störr - Klinik für Neurochirurgie, Universitätsklinikum Regensburg
  • A. Lohmeier - Klinik für Neurochirurgie, Universitätsklinikum Regensburg
  • M. Friedrich - Klinik für Neurochirurgie, Universitätsklinikum Regensburg
  • A. Brawanski - Klinik für Neurochirurgie, Universitätsklinikum Regensburg

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP08-03

DOI: 10.3205/09dgnc331, URN: urn:nbn:de:0183-09dgnc3316

Veröffentlicht: 20. Mai 2009

© 2009 Proescholdt 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: In craniopharyngiomas extensive cyst formation can cause pressure on the adjacent brain which is related to significant morbidity. The molecular basis of cyst formation is currently unknown. Carbonic anhydrase IX (CA IX) is a hypoxia-inducible enzyme which is involved in fluid production and cyst formation. We wanted to investigate whether CA IX is overexpressed in craniopharyngiomas and whether CA IX expression levels correlate with the extent of cyst formation. To understand the regulation of CA IX expression, we investigated the presence of hypoxia inducible factor 1 alpha (HIF-1 alpha) as well as Vascular Endothelial Growth Factor (VEGF) as an alternative hypoxia-regulated gene. Since CA IX is under the control of the tumor suppressor protein P53, we evaluated the p53 mutation status of the tumors.

Methods: We analyzed tissue from 20 craniopharyngioma patients, 10 male (50%) and 10 female (50%), with a mean age of 47.2 years (range: 12–81). CA IX expression was investigated by in situ hybridization and immunohistochemistry. CA IX expression was graded by using a four-grade scale. Cyst volume was quantified volumetrically utilizing Brain Lab Iplan Cranio software. To analyze the mechanism of CA IX up-regulation, immunohistochemical staining for HIF-1 alpha as well as for VEGF was performed. Informative tumor tissue was obtained by laser capture microdissection, and the p53 status was investigated by SSCP-analysis and direct sequencing.

Results: 85% of all craniopharyngioma cases showed a significant CA IX expression. The extent of CA IX expression significantly correlated with the cyst volume (p<0.01; ANOVA on ranks). HIF-1 alpha expression was mostly absent in the tissue samples. VEGF expression was present in a subset of cases (20%) on a moderate level. The p53 mutation status did not correlate with the extent of CA IX expression.

Conclusions: CA IX is significantly upregulated in the majority of the analyzed craniopharyngioma cases. The mechanism of CA IX expression remains unknown; we did not detect significant levels of HIF-1 alpha or VEGF, which argues against tissue hypoxia as a major regulating factor. Furthermore, the p53 status did not correlate with the CA IX expression levels. Cyst volume was significantly correlated with the CA IX expression, suggesting a functional role of CA IX in the process of cyst formation. These results indicate that CA IX may be a potential target for adjuvant treatment in patients with cystic craniopharyngiomas.