Department of Neurosurgery, Puerta de Hierro University Hospital, C/Manuel de Falla 1, Majadahonda, 28222, Madrid, Spain.
Department of Neurosurgery, La Princesa University Hospital, Madrid, Spain.
Pituitary. 2018 Aug;21(4):431-442. doi: 10.1007/s11102-018-0890-6.
The growing interest in the molecular and genetic alterations of craniopharyngiomas (CPs) is embodied in recent studies revealing insights into the CP tumorigenesis and identifying novel molecular pathways amenable of targeted therapies. The actual impact of this new information, however, remains inconclusive.
We present a comprehensive review of the accumulated knowledge on molecular biology of CPs and a critical analysis on the strengths and weaknesses of the studies focused on CP molecular/genetic alterations published to date.
A thorough analysis of the alterations of β-catenin/CTNNB1 and BRAF genes investigated in 1123 CP cases included in 27 studies, showed that, on average, CTNNB1 mutations were present in two-thirds of adamantinomatous CPs and BRAF mutations in 90% of papillary CPs. Their role as oncogenic drivers has not been well established. Although rare, coexistence of both mutations may occur. The involvement of pituitary stem cells in human CP tumorigenesis is still uncertain. Expression of stem markers in human CP samples predominantly occurred along the CP border in contact with brain tissue. Finally, none of the various molecular alterations which have been proposed as markers for CP recurrence can be used today as reliable predictors of the CP behavior.
The isolated evaluation of CPs' molecular or genetic profiles that do not take into consideration fundamental pathological and therapeutic factors, specifically the tumor topography and the degree of tumor removal, may actually generate confusion regarding the reliability of some biomarkers to predict the CP biological behavior.
人们对颅咽管瘤（CPs）分子和遗传改变的兴趣日益浓厚，这体现在最近的研究中，这些研究揭示了 CP 肿瘤发生的机制，并确定了新的分子途径，使其能够进行靶向治疗。然而，这些新信息的实际影响仍不确定。
我们对 CPs 的分子生物学积累知识进行了全面综述，并对迄今为止发表的关于 CP 分子/遗传改变的研究的优缺点进行了批判性分析。
对 27 项研究中纳入的 1123 例 CP 病例中β-连环蛋白/CTNNB1 和 BRAF 基因改变的深入分析表明，平均而言，CTNNB1 突变存在于三分之二的造釉细胞瘤中，而 BRAF 突变存在于 90%的乳头瘤中。它们作为致癌驱动因素的作用尚未得到很好的证实。虽然罕见，但可能同时存在这两种突变。垂体干细胞在人类 CP 肿瘤发生中的作用仍不确定。在人类 CP 样本中，干细胞标志物的表达主要沿着与脑组织接触的 CP 边界发生。最后，目前还没有任何被提议作为 CP 复发标志物的各种分子改变可以作为 CP 行为的可靠预测指标。
孤立地评估 CPs 的分子或遗传谱，如果不考虑基本的病理和治疗因素，特别是肿瘤的位置和肿瘤的切除程度，可能会对一些生物标志物预测 CP 生物学行为的可靠性产生混淆。
