title: Nuclear beta-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas.
abstract: 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.
authors.affiliation: Department of Neuropathology, Friedrich-Alexander University Erlangen-Nuremberg, Krankenhausstrasse 8-10, 91054 Erlangen, Germany. rolf.buslei@neuropatho.imed.uni-erlangen.de
authors.forename: Rolf
authors.initials: R
authors.lastname: Buslei
authors.forename: Annett
authors.initials: A
authors.lastname: Hölsken
authors.forename: Bernd
authors.initials: B
authors.lastname: Hofmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kreutzer
authors.forename: Florian
authors.initials: F
authors.lastname: Siebzehnrubl
authors.forename: Volkmar
authors.initials: V
authors.lastname: Hans
authors.forename: Falk
authors.initials: F
authors.lastname: Oppel
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fahlbusch
authors.forename: Ingmar
authors.initials: I
authors.lastname: Blümcke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000378:metabolism* / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004848:Epithelium / Q000254:growth & development* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D053533:Keratin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009024:Morphogenesis / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053538:Keratin-18; D053533:Keratin-8; D051176:beta Catenin