Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma.
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.
Kato
Keisuke
K
Division of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.
Nakatani
Yukio
Y
Kanno
Hiroshi
H
Inayama
Yoshiyuki
Y
Ijiri
Rieko
R
Nagahara
Noriyuki
N
Miyake
Tetsumi
T
Tanaka
Mio
M
Ito
Yumi
Y
Aida
Noriko
N
Tachibana
Katsuhiko
K
Sekido
Ken-ichi
K
Tanaka
Yukichi
Y
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
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