title: Expression of carbonic anhydrase IX in craniopharyngiomas.
abstract: OBJECTIVE
  In craniopharyngiomas, cystic growth causes pressure on vital structures of the adjacent brain, leading to significant morbidity. However, the molecular pathogenesis of this cyst formation remains unknown. Carbonic anhydrase IX (CA IX) is a tumor-associated, hypoxia-inducible enzyme, which can cause fluid production and development of cysts. The authors investigated CA IX expression in craniopharyngiomas and its correlation with the extent of cyst formation. In addition, the major pathways of CA IX regulation, hypoxia and p53 mutation, were analyzed.
  
  
  METHODS
  Expression of CA IX was analyzed in 20 craniopharyngioma patients by means of in situ hybridization and immunohistochemistry. Preoperative imaging was used to quantify cyst volume. To analyze putative hypoxic induction of CA IX, immunohistochemical staining for HIF-1α and VEGF was performed. Since p53 negatively regulates CA IX expression, we also analyzed the tumors for p53 mutation by direct sequencing.
  
  
  RESULTS
  Significant CA IX was found in 85% of the 20 cases. The extent of CA IX expression was significantly correlated with cyst volume. HIF-1α expression was largely absent in all tissue samples, whereas moderate VEGF expression was present in a subset of cases but without correlation to cyst volume. No p53 mutation was found in any of the analyzed tumors.
  
  
  CONCLUSIONS
  Carbonic anhydrase IX, which is virtually absent in normal brain, is significantly upregulated in craniopharyngiomas and shows a significant association with cyst size. The mechanisms of regulation remain unknown, since neither hypoxia nor p53 appears to play a role. These results indicate that inhibition of CA IX may be a potential target for the adjuvant treatment in patients with cystic craniopharyngiomas.
authors.affiliation: Department of Neurosurgery, University Regensburg Medical Center, Regensburg, Germany. martin.proescholdt@klinik.uni-regensburg.de
authors.forename: Martin
authors.initials: M
authors.lastname: Proescholdt
authors.forename: Marsha
authors.initials: M
authors.lastname: Merrill
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Stoerr
authors.forename: Annette
authors.initials: A
authors.lastname: Lohmeier
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Alexander
authors.initials: A
authors.lastname: Brawanski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases