title: Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma.
abstract: This study concerns the significance of nuclear/cytoplasmic expression of beta-catenin and mutation of the beta-catenin gene in craniopharyngiomas. Fourteen adamantinomatous type and one squamous papillary type craniopharyngiomas were studied. Histologically, 13 of 14 adamantinomatous type craniopharyngiomas showed typical features, ie mixtures of 'palisading cells', 'stellate cells', and 'ghost cells'. In addition, 'whorl-like arrays' of epithelial cells were frequently observed in the areas of stellate cells. On immunohistochemistry, all typical adamantinomatous type craniopharyngiomas showed nuclear/cytoplasmic expression of beta-catenin predominantly in cohesive cells within the whorl-like arrays and in cells transitional towards ghost cells, where immunoreactivity for Ki-67 was almost absent. The cohesive cells in the whorl-like arrays also demonstrated loss of cytokeratin isoform expression. Using direct sequencing of amplified nucleic acids, nine of the 13 typical adamantinomatous type craniopharyngiomas with nuclear beta-catenin accumulation showed heterozygous one-base substitution mutation of the beta-catenin gene. The other unusual adamantinomatous type and squamous papillary type craniopharyngiomas showed no obvious nuclear/cytoplasmic beta-catenin immunoreactivity and no mutation of the beta-catenin gene, suggesting molecular heterogeneity. These findings suggest that the pathogenesis of typical adamantinomatous type craniopharyngioma is associated with abnormalities of Wnt signalling that act as a morphogenetic signal towards whorl-like arrays and ghost cells rather than as simple proliferation stimuli.
authors.affiliation: Division of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kato
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanno
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Inayama
authors.forename: Rieko
authors.initials: R
authors.lastname: Ijiri
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagahara
authors.forename: Tetsumi
authors.initials: T
authors.lastname: Miyake
authors.forename: Mio
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ito
authors.forename: Noriko
authors.initials: N
authors.lastname: Aida
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tachibana
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Sekido
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin