Expression of carbonic anhydrase IX in craniopharyngiomas Laboratory investigation

Proescholdt, Martin and Merrill, Marsha and Stoerr, Eva-Maria and Lohmeier, Annette and Dietmaier, Wolfgang and Brawanski, Alexander (2011) Expression of carbonic anhydrase IX in craniopharyngiomas Laboratory investigation. JOURNAL OF NEUROSURGERY, 115 (4). pp. 796-801. ISSN 0022-3085, 1933-0693

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Abstract

Object. 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-1 alpha 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-1 alpha 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. (DOI: 10.3171/2011.6.JNS1168)

Item Type: Article
Uncontrolled Keywords: GENOMIC HYBRIDIZATION ANALYSIS; ENDOTHELIAL GROWTH-FACTOR; LINDAU TUMOR-SUPPRESSOR; RENAL-CELL CARCINOMA; ASTROCYTIC TUMORS; POOR-PROGNOSIS; HYPOXIA; GENE; PATHOGENESIS; PH; cyst formation; hypoxia; p53; angiogenesis; carbonic anhydrase IX; oncology
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Neurochirurgie
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 Jun 2020 07:15
Last Modified: 02 Jun 2020 07:15
URI: https://pred.uni-regensburg.de/id/eprint/20078

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