Artikel
Abundant mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other variants of intra- and suprasellar neoplasms
Nachweis zahlreicher Mutationen von b-catenin in adamantinösen Craniopharyngiomen im Gegensatz zu anderen intra- und suprasellären Neoplasien
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
Text
Objective
Dysregulation of the Wnt signaling pathway contributes to developmental abnormalities and carcinogenesis of solid tumors. Recently, a possible role of β-catenin has been proposed for adamantinomatous craniopharyngiomas (CPs) whereas its involvement in the formation of other variants of intra- and suprasellar neoplasms remains controversial.
Methods
In this study we examined b-catenin and APC by mutational analysis in a large series of tumors and cysts of the sellar region: pituitary adenomas (PA, n=60), craniopharyngiomas (CP, n=65), arachnoidal cysts (AC, n=8), Rathke´s cleft cysts (RC, n=10) and xanthogranulomas (XG, n=6). The cellular expression pattern of β-catenin was analysed using immunohistochemistry.
Results
Whereas APC mutations were not detectable in either tumor entity, β-catenin mutations were present in 77% of CPs, exclusively of the adamantinomatous subtype. All mutations affected exon 3 encoding the degradation targeting box of β-catenin leading to accumulation of nuclear β-catenin protein. In addition, a novel 81bp deletion of this exonic region was detected. Immunohistochemical analysis confirmed a shift from membrane-bound to nuclear accumulation of β-catenin in 94% of the adamantinomatous CP subtype, which was never observed in any of the other tumor entities.
Conclusions
The restricted immunohistochemical distribution pattern of nuclear β-catenin accumulation is compatible with a role during morphogenesis, i.e. the formation of whorls and invasion towards brain parenchyma. The abundance of activating mutations in the β-catenin gene serves as a molecular hallmark in the pathogenesis of adamantinomatous craniopharyngiomas, distinct from papillary craniopharyngiomas and other frequent neoplasms of the sellar region.