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Nuclear beta-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas

Buslei, Rolf, Hoelsken, Annett, Hofmann, Bernd, Kreutzer, Juergen, Siebzehnrubl, Florian, Hans, Volkmar, Oppel, Falk, Buchfelder, Michael, Fahlbusch, Rudolf and Bluemcke, Ingmar 2007. Nuclear beta-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas. Acta Neuropathologica 113 (5) , pp. 585-590.

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Abstract

Activation of the Wnt/wingless signalling cascade is a key mechanism in developmental morphogenesis, whereas aberrant nuclear accumulation of β-catenin in adult tissues seems to be associated with neoplastic transformation and tumour progression. Adamantinomatous craniopharyngiomas carry activating mutations in exon 3 of the β-catenin gene, which results in a distinct pattern of nuclear β-catenin accumulation in up to 95% of respective tumour specimens. To better characterise the impact of nuclear β-catenin aggregation in these neoplasms, we systematically examined epithelial differentiation and cell cycle-associated molecules in accumulating compared to non-accumulating tumour cell clusters using a cohort of 65 adamantinomatous craniopharyngiomas. Monoclonal antibodies directed against cytokeratins 5/6 (CK5/6) were utilised to differentiate squamous from simple epithelium, the latter being identified by immunoreactivity for cytokeratins 8 and 18 (CK8/CK18). Intriguingly, nuclear β-catenin accumulation in whorl-like tumour cell clusters was always associated with a distinct CK8 and CK18 immunoreactivity, whereas surrounding non-accumulating tumour cells showed exclusively squamous differentiation indicated by CK5/6 expression. In addition, a low proliferation activity combined with an increased expression of p21WAF1/CIP1, a key control protein of the cell cycle, was observed in β-catenin accumulating cells. Our data support an impact of nuclear β-catenin on different cytoarchitectural and epithelial differentiation patterns in adamantinomatous craniopharyngiomas.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Publisher: Springer Verlag
ISSN: 0001-6322
Last Modified: 04 Jun 2017 06:31
URI: http://orca-mwe.cf.ac.uk/id/eprint/61402

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