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与儿童相比,成人的毛细胞型星形细胞瘤中mTOR激活增加。

mTOR activation is increased in pilocytic astrocytomas from older adults compared with children.

作者信息

Johnson Mahlon D, O'Connell Mary, Walter Kevin, Silberstein Howard

机构信息

Department of Pathology, Division of Neuropathology, University of Rochester School of Medicine, Rochester, New York, USA.

Department of Neurosurgery, University of Rochester School of Medicine, Rochester, New York, USA.

出版信息

Surg Neurol Int. 2017 May 26;8:85. doi: 10.4103/sni.sni_367_16. eCollection 2017.

Abstract

BACKGROUND

Recent studies suggest that the behavior and biology of WHO grade I pilocytic astrocytomas (PAs) in adults is different than that associated with grade I PAs in children.

METHODS

We evaluated Ki-67 labeling, BRAF abnormalities, isocitrate dehydrogenase R132 immunoreactivity phosphorylation (activation) of p44/42 mitogen activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) in formalin-fixed tissue from 21 adult (18 years or older, mean age 37 years) and 10 children (mean age 9.4 years) WHO grade I PAs.

RESULTS

The mean Ki-67 labeling was 4.8% in adults and 3.8% in children. There was no significant difference between Ki-67 labeling in children and adults or either subgroups of adults. No differences were found in phospho p44/42MAPK in adult subgroups (18-33 years and 34 and older) compared to children. Activation/phosphorylation of mTOR was biphasic in adults being significantly lower than children in young adults but significantly higher than children in older adults (age 34 and older).

CONCLUSIONS

Identifying mTOR phosphorylation/activation may represent a difference in biology and a new marker to guide chemotherapy with recently approved mTOR inhibitors.

摘要

背景

近期研究表明,成人世界卫生组织(WHO)I级毛细胞型星形细胞瘤(PA)的行为和生物学特性与儿童I级PA不同。

方法

我们评估了21例成人(18岁及以上,平均年龄37岁)和10例儿童(平均年龄9.4岁)WHO I级PA的福尔马林固定组织中的Ki-67标记、BRAF异常、异柠檬酸脱氢酶R132免疫反应性、p44/42丝裂原活化蛋白激酶(MAPK)的磷酸化(激活)以及雷帕霉素哺乳动物靶点(mTOR)。

结果

成人的平均Ki-67标记率为4.8%,儿童为3.8%。儿童与成人或成人亚组之间的Ki-67标记率无显著差异。与儿童相比,成人亚组(18 - 33岁和34岁及以上)的磷酸化p44/42MAPK无差异。mTOR的激活/磷酸化在成人中呈双相性,在年轻成人中显著低于儿童,但在老年成人(34岁及以上)中显著高于儿童。

结论

确定mTOR磷酸化/激活可能代表生物学差异以及一种新的标志物,可用于指导使用最近批准的mTOR抑制剂进行化疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75e0/5461564/64d2e523c06b/SNI-8-85-g002.jpg

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