PROP1 and CTNNB1 expression in adamantinomatous craniopharyngiomas with or without β-catenin mutations

INTRODUCTION: 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 OBJECTIVES: 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 percent of the adamantinomatous craniopharyngiomas samples. Evidence of β-catenin gene overexpression was found in 71 percent of the tumors with β-catenin mutations and in 40 percent 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. CONCLUSION: 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 bcatenin 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.

Mania associada ao uso de glicocorticóides para oftalmopatia de Graves: relato de caso / Mania associated with the use of glucocorticoids for Graves' ophthalmopathy: case report

O hipertireoidismo é uma síndrome clínica de hipermetabolismo caracterizada por várias manifestações sistêmicas, inclusive neuropsiquiátricas. Além do mais, a doença de Graves, uma das formas mais comuns de hipertireoidismo, pode cursar com uma forma específica de oftalmopatia. Os glicocorticóides são freqüentemente utilizados no tratamento desses sintomas oculares da doença. Por outro lado, encontra-se bem estabelecido que os corticóides podem causar complicações psiquiátricas. Relatamos um caso de uma paciente com tireotoxicose pela doença de Graves que, durante o seu acompanhamento, evoluiu com quadro compatível com síndrome maníaca associado à introdução de corticosteróide para controle da oftalmopatia. Discutimos as manifestações psiquiátricas apresentadas pela paciente assim como analisamos fatores associados ao desenvolvimento da síndrome maníaca nessa condição clínica.