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Journal of Neurosurgery 2018-Aug

Clinical and biological significance of adamantinomatous craniopharyngioma with CTNNB1 mutation.

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Takuma Hara
Hiroyoshi Akutsu
Shingo Takano
Hiroyoshi Kino
Eiichi Ishikawa
Shuho Tanaka
Hidetaka Miyamoto
Noriaki Sakamoto
Keiichiro Hattori
Mamiko Sakata-Yanagimoto

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Abstracto

OBJECTIVE The Wnt/β-catenin signaling pathway is strongly implicated in the pathogenesis of adamantinomatous craniopharyngioma (adaCP). However, there is no evidence that the CTNNB1 mutation activates the target gene of Wnt/β-catenin signaling, and it is unknown whether it affects the tumorigenesis of adaCP. To assess the effect of the CTNNB1 mutation of adaCP, the authors analyzed the correlation between the mutation and clinical, radiological, pathological, and biological findings. METHODS Between 2003 and 2015, 42 patients (24 male and 18 female, median age 42 years) with either papillary craniopharyngioma (papCP) or adaCP underwent tumor resection at the authors' institution. BRAF V600E and CTNNB1 in papCP and adaCP samples were sequenced by next-generation sequencing and the Sanger method, and mRNA expression levels of Axin2 and BMP4 were evaluated by RT-PCR. Axin2, BMP4, β-catenin, and BRAF expression were evaluated by immunohistochemistry. Other data were collected from clinical reports. RESULTS The BRAF V600E mutation was detected in all 10 cases of papCP (100%). CTNNB1 exon 3 mutations were detected in 21 of 31 (68%) cases of adaCP, excluding 1 case for which there were no available sequence data. The mRNA expression level of Axin2 was significantly higher in adaCPs with a CTNNB1 mutation than in those without (p < 0.05). The immunohistochemical findings of Axin2 and BMP4 did not correlate with CTNNB1 mutation positivity. When patients who received adjuvant radiation therapy were excluded, progression-free survival was shorter in the mutation-positive group than in the mutation-negative group (log-rank test, p = 0.031). Examination of clinical characteristics and immunohistochemical findings of adaCPs showed that there was no significant correlation between CTNNB1 mutation positivity and age, sex, tumor volume, gross-total resection, optic tract edema, calcification, or T1 signal intensity of cyst fluid on MRI, β-catenin, and MIB-1 index. CONCLUSIONS These results raise the possibility that the CTNNB1 mutation in adaCP may be associated with disease recurrence, and genes related to the Wnt/β-catenin signaling pathway might represent a therapeutic target.

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