TY - JOUR AU - Jucá, Carlos Eduardo Barros; Colli, Leandro Machado; Martins, Clarissa Silva; Campanini, Marina Lanciotti; Paixão, Beatriz; Jucá, Renata Viana; Saggioro, Fabiano Pinto; de Oliveira, Ricardo Santos; Moreira, Ayrton Custódio; Machado, Hélio Rubens; Neder, Luciano; Antonini, Sonir Rauber; de Castro, Margaret TI - Impact of the Canonical Wnt Pathway Activation on the Pathogenesis and Prognosis of Adamantinomatous Craniopharyngiomas SN - 0018-5043 SN - 1439-4286 PY - 2018 JO - Horm Metab Res JF - Hormone and Metabolic Research LA - EN VL - 50 IS - 07 SP - 575 EP - 581 ET - 2018/04/06 DA - 2018/07/10 KW - craniopharyngioma KW - Wnt pathway KW - β-catenin KW - prognosis KW - recurrence AB - 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. PB - © Georg Thieme Verlag KG DO - 10.1055/a-0593-5956 UR - http://www.thieme-connect.com/products/ejournals/abstract/10.1055/a-0593-5956 ER -