title: Differential Expression of Stem Cell Markers in Human Adamantinomatous Craniopharyngioma and Pituitary Adenoma.
abstract: OBJECTIVE
  Although craniopharyngioma (CP) is histologically benign, it is a pituitary tumour that grows rapidly and often recurs. Adamantinomatous CP (ACP) was associated with an activating mutation in β-catenin, and it has been postulated that pituitary stem cells might play a role in oncogenesis in human ACP. Stem cells have also been identified in pituitary adenoma. Our aim was to characterize the expression pattern of ABCG2, CD44, DLL4, NANOG, NOTCH2, POU5F1/OCT4, SOX2, and SOX9 stem cell markers in human ACP and pituitary adenoma.
  
  
  RESULTS
  We studied 33 patients (9 ACP and 24 adenoma) using real-time quantitative PCR (RT-qPCR) and immunohistochemistry. SOX9 was up-regulated in ACP, exhibiting positive immunostaining in the epithelium and stroma, with the highest expression in patients with recurrence. CD44 was overexpressed in ACP as confirmed by immunohistochemistry. SOX2 did not significantly differ among the tumour types. The RT-qPCR array showed an increased expression of MKI67,OCT4/POU5F1, and DLL4 in all tumours. NANOG was decreased in ACP. ABCG2 was down-regulated in most of the tumours. NOTCH2 was significantly decreased in the adenomas.
  
  
  CONCLUSIONS
  Our results confirm the presence of stem cell markers in human pituitary tumours as well as the different expression patterns of ACP and adenoma. These findings suggest that ACP may originate from a more undifferentiated cell cluster. Additionally, SOX9 immunodetection in the stroma and the highest expression levels related to the relapse of patients suggest a contribution to the aggressive behaviour and high recurrence of this tumour type.
authors.affiliation: Laboratório de Hormônios e Genética Molecular - LIM/42, Divisão de Endocrinologia, FMUSP, Brasília, Brazil.
authors.forename: Claudia Veiga
authors.initials: CV
authors.lastname: Chang
authors.forename: Ricardo Vieira
authors.initials: RV
authors.lastname: Araujo
authors.forename: Cinthya Santos
authors.initials: CS
authors.lastname: Cirqueira
authors.forename: Carolina Maria Gomes
authors.initials: CM
authors.lastname: Cani
authors.forename: Hamilton
authors.initials: H
authors.lastname: Matushita
authors.forename: Valter Angelo Sperling
authors.initials: VA
authors.lastname: Cescato
authors.forename: Maria Candida Barisson Villares
authors.initials: MC
authors.lastname: Fragoso
authors.forename: Marcello Delano
authors.initials: MD
authors.lastname: Bronstein
authors.forename: Maria Claudia Nogueira
authors.initials: MC
authors.lastname: Zerbini
authors.forename: Berenice Bilharinho
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Luciani Renata
authors.initials: LR
authors.lastname: Carvalho
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058953:Neural Stem Cells / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D055758:SOX9 Transcription Factor / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C527782:SOX2 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D055748:SOXB1 Transcription Factors