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- Title
Nuclear β-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas.
- Authors
Buslei, Rolf; Hölsken, Annett; Hofmann, Bernd; Kreutzer, Jürgen; Siebzehnrubl, Florian; Hans, Volkmar; Oppel, Falk; Buchfelder, Michael; Fahlbusch, Rudolf; Blümcke, Ingmar
- 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.
- Subjects
MORPHOGENESIS; INTRACRANIAL tumors; EPITHELIAL cells; MONOCLONAL antibodies; TUMOR growth; CANCER cells; IMMUNOGLOBULINS; CELL cycle
- Publication
Acta Neuropathologica, 2007, Vol 113, Issue 5, p585
- ISSN
0001-6322
- Publication type
Article
- DOI
10.1007/s00401-006-0184-3