Nuclear beta-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas
| Autor: | J Kreutzer, Florian A. Siebzehnrubl, Bernd Hofmann, Volkmar Hans, Ingmar Blümcke, Rolf Buslei, Falk Oppel, Annett Hölsken, Michael Buchfelder, Rudolf Fahlbusch |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Cyclin-Dependent Kinase Inhibitor p21 Male Beta-catenin Adolescent Squamous Differentiation Cell Morphogenesis Epithelium Pathology and Forensic Medicine Cellular and Molecular Neuroscience Exon Craniopharyngioma medicine Humans Neoplastic transformation Child beta Catenin Aged Cell Nucleus biology Keratin-18 Keratin-8 Wnt signaling pathway Cell Differentiation Cell cycle Middle Aged Cell biology Gene Expression Regulation Neoplastic medicine.anatomical_structure Child Preschool biology.protein Female Neurology (clinical) |
| Zdroj: | Acta neuropathologica. 113(5) |
| ISSN: | 0001-6322 |
| Popis: | Activation of the Wnt/wingless signalling cascade is a key mechanism in developmental morphogenesis, whereas aberrant nuclear accumulation of beta-catenin in adult tissues seems to be associated with neoplastic transformation and tumour progression. Adamantinomatous craniopharyngiomas carry activating mutations in exon 3 of the beta-catenin gene, which results in a distinct pattern of nuclear beta-catenin accumulation in up to 95% of respective tumour specimens. To better characterise the impact of nuclear beta-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 beta-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 p21(WAF1/CIP1), a key control protein of the cell cycle, was observed in beta-catenin accumulating cells. Our data support an impact of nuclear beta-catenin on different cytoarchitectural and epithelial differentiation patterns in adamantinomatous craniopharyngiomas. |
| Databáze: | OpenAIRE |
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