title: PROP1 and CTNNB1 expression in adamantinomatous craniopharyngiomas with or without β-catenin mutations.
abstract: BACKGROUND
  Activating mutations in exon 3 of the β-catenin gene are involved in the pathogenesis of adamantinomatous craniopharyngiomas. Recently, the interaction between β-catenin and PROP1 has been shown to be responsible for pituitary cell lineage determination. We hypothesized that dysregulated PROP1 expression could also be involved in the pathogenesis of craniopharyngiomas
  
  
  OBJECTIVE
  To determine whether dysregulated gene expression was responsible for tumor pathogenesis in adamantinomatous craniopharyngiomas, the β-catenin gene was screened for mutations, and the expression of the β-catenin gene and PROP1 was evaluated. β-catenin gene was amplified and sequenced from 14 samples of adamantinomatous craniopharyngiomas. PROP1 and β-catenin gene expression was assessed by real-time RT-PCR from 12 samples, and β-catenin immunohistochemistry was performed on 11 samples.
  
  
  RESULTS
  Mutations in the β-catenin gene were identified in 64% of the adamantinomatous craniopharyngiomas samples. Evidence of β-catenin gene overexpression was found in 71% of the tumors with β-catenin mutations and in 40% of the tumors without mutations, and β-catenin immunohistochemistry revealed a nuclear staining pattern for each of the analyzed samples. PROP1 expression was undetectable in all of the tumor samples.
  
  
  CONCLUSIONS
  We found evidence of β-catenin gene overexpression in the majority of adamantinomatous craniopharyngiomas, and we also detected a nuclear β-catenin staining pattern regardless of the presence of a β-catenin gene mutation. These results suggest that WNT signaling activation plays an important role in the pathogenesis of adamantinomatous craniopharyngiomas. Additionally, this study was the first to evaluate PROP1 expression in adamantinomatous craniopharyngiomas, and the absence of PROP1 expression indicates that this gene is not involved in the pathogenesis of this tumor, at least in this cohort.
authors.affiliation: Laboratório de Hormônios e Genética Molecular, Unidade de Endocrinologia do Desenvolvimento, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. carolinacani@gmail.com
authors.forename: Carolina M G
authors.initials: CM
authors.lastname: Cani
authors.forename: Hamilton
authors.initials: H
authors.lastname: Matushita
authors.forename: Luciani R S
authors.initials: LR
authors.lastname: Carvalho
authors.forename: Ibere C
authors.initials: IC
authors.lastname: Soares
authors.forename: Luciana P
authors.initials: LP
authors.lastname: Brito
authors.forename: Madson Q
authors.initials: MQ
authors.lastname: Almeida
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonça
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D051153:Wnt Proteins; D051176:beta Catenin
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