Dysregulation of the Wnt signalling pathway contributes to developmental abnormalities and
carcinogenesis of solid tumours. Here, we examined
beta-catenin and
adenomatous polyposis coli (APC) by mutational analysis in
pituitary adenomas (n=60) and a large series of
craniopharyngiomas (n=41). Furthermore, the expression pattern of
beta-catenin was immunohistochemically analysed in a cohort of tumours and
cysts of the sellar region including
pituitary adenomas (n=58),
craniopharyngiomas (n=57), arachnoidal
cysts (n=8),
Rathke's cleft cysts (n=10) and xanthogranulomas (n=6). Whereas APC mutations were not detectable in any tumour entity,
beta-catenin mutations were present in 77% of
craniopharyngiomas, exclusively of the adamantinomatous subtype. All mutations affected exon 3, which encodes the degradation targeting box of
beta-catenin compatible with an accumulation of nuclear
beta-catenin protein. In addition, a novel 81-bp deletion of this exonic region was detected in one case. Immunohistochemical analysis confirmed a shift from membrane-bound to nuclear accumulation of
beta-catenin in 94% of the adamantinomatous tumours. Aberrant distribution patterns of
beta-catenin were never observed in the other tumour entities under study. We conclude that
beta-catenin mutations and/or nuclear accumulation serve as diagnostic hallmarks of the adamantinomatous variant, setting it apart from the papillary variant of
craniopharyngioma.