Pituitary Unit of the Division of Neurosurgery, IRCCS San Raffaele, University Vita-Salute, Milan, MI, Italy.
Istituto Auxologico Italiano IRCCS, Neuroendocrine Research Laboratory, Milan, MI, Italy.
Endocrine. 2019 Feb;63(2):240-246. doi: 10.1007/s12020-018-1776-0. Epub 2018 Oct 12.
somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been described in patients with Cushing's disease (CD). The aim of the study is to verify whether USP8 mutation may predict early and late outcome of pituitary surgery in patients with CD operated at a single institution.
We performed a retrospective genetic analysis of 92 adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Specimens were screened for USP8 hotspot mutations in the exon 14 with Sanger sequencing. Hormonal and surgical data were compared between USP8 variant carriers and wild-type tumors.
USP8 variants were detected in 22 adenomas (23.9%) with higher prevalence in women (28.9% vs. 5.3% in men; p < 0.05). No significant difference in hormonal levels and tumoral features in relation to USP8 status was observed. Interestingly, USP8-variant carriers were more likely to achieve surgical remission than wild-type adenomas (100% vs. 75.7%; p = 0.01). Conversely, recurrence of CD occurred in 23% of USP8-mutated patients and in 13% of patients with wild-type adenoma. The recurrence-free survival did not differ significantly between the two groups (p = 0.42).
ACTH-secreting pituitary adenomas carrying somatic USP8 mutations are associated with a greater likelihood of surgical remission in patients operated by a single neurosurgeon. Recurrence rates are not related with USP8-variant status.
最近在库欣病（CD）患者中描述了泛素特异性蛋白酶 8（USP8）基因的体细胞突变。本研究旨在验证USP8 突变是否可以预测在单一机构接受手术的 CD 患者的垂体手术的早期和晚期结果。
我们对 92 例促肾上腺皮质激素（ACTH）分泌性垂体腺瘤进行了回顾性遗传分析。使用 Sanger 测序对 USP8 外显子 14 的热点突变进行了筛查。比较了 USP8 变异携带者和野生型肿瘤的激素和手术数据。
在 22 个腺瘤中检测到 USP8 变体（23.9％），女性的发生率更高（28.9％比男性的 5.3％；p <0.05）。与 USP8 状态无关，激素水平和肿瘤特征无明显差异。有趣的是，与野生型腺瘤相比，USP8 变异携带者更有可能实现手术缓解（100％比 75.7％；p = 0.01）。相反，CD 的复发发生在 23％的 USP8 突变患者和 13％的野生型腺瘤患者中。两组之间的无复发生存率无显着差异（p = 0.42）。
由单一神经外科医生手术的患者中，携带体细胞 USP8 突变的 ACTH 分泌性垂体腺瘤与更大的手术缓解可能性相关。复发率与 USP8 变异状态无关。
