Horm Metab Res 2018; 50(07): 575-581
DOI: 10.1055/a-0593-5956
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Impact of the Canonical Wnt Pathway Activation on the Pathogenesis and Prognosis of Adamantinomatous Craniopharyngiomas

Carlos Eduardo Barros Jucá*
1  Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Leandro Machado Colli*
2  Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Clarissa Silva Martins
2  Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Marina Lanciotti Campanini
2  Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Beatriz Paixão
2  Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Renata Viana Jucá
3  Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Fabiano Pinto Saggioro
3  Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Ricardo Santos de Oliveira
1  Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Ayrton Custódio Moreira
2  Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Hélio Rubens Machado
1  Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Luciano Neder
3  Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Sonir Rauber Antonini
4  Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Margaret de Castro
2  Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
› Author Affiliations
Further Information

Publication History

received 20 August 2017

accepted 07 March 2018

Publication Date:
06 April 2018 (online)

Abstract

CTNNB1 mutations and abnormal β-catenin distribution are associated with the pathogenesis of adamantinomatous craniopharyngioma (aCP). We evaluated the expression of the canonical Wnt pathway components in aCPs and its association with CTNNB1 mutations and tumor progression. Tumor samples from 14 aCP patients and normal anterior pituitary samples from eight individuals without pituitary disease were studied. Gene expression of Wnt pathway activator (WNT4), inhibitors (SFRP1, DKK3, AXIN1, and APC), transcriptional activator (TCF7), target genes (MYC, WISP2, and, CDH1), and Wnt modulator (TP53) was evaluated by qPCR. β-Catenin, MYC, and WISP2 expression was determined by immunohistochemistry (IHC). The transcription levels of all genes studied, except APC, were higher in aCPs as compared to controls and TCF7 mRNA levels correlated with CTNNB1 mutation. CDH1 mRNA was overexpressed in tumor samples of patients with disease progression in comparison to those with stable disease. β-Catenin was positive and aberrantly distributed in 11 out of 14 tumor samples. Stronger β-catenin immunostaining associated positively with tumor progression. MYC positive staining was found in 10 out of 14 cases, whereas all aCPs were negative for WISP2. Wnt pathway genes were overexpressed in aCPs harboring CTNNB1 mutations and in patients with progressive disease. Recurrence was associated with stronger staining for β-catenin. These data suggest that Wnt pathway activation contributes to the pathogenesis and prognosis of aCPs.

* These authors contributed equally to the work