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NF2 基因突变频发与砂粒体型脑膜瘤脊柱好发部位和不良预后相关。

Association of frequent NF2 mutations with spinal location predominance and worse outcomes in psammomatous meningiomas.

机构信息

1Departments of Neurosurgery and.

2Institute of Neurosurgery, Fudan University, Shanghai, China.

出版信息

J Neurosurg. 2024 Mar 29;141(3):593-601. doi: 10.3171/2024.1.JNS232450. Print 2024 Sep 1.

Abstract

OBJECTIVE

Psammomatous meningiomas (PMs) are a rare histological subtype of meningioma but are rather frequent in spinal meningiomas. The authors aimed to analyze the incidence, clinical features, molecular alterations, long-term outcomes, and prognostic factors of PMs.

METHODS

In total, 151 patients with PMs were included in this study. Clinical characteristics, molecular alterations, and progression-free survival (PFS) were analyzed in PMs. Clinical characteristics were compared between PMs and other WHO grade 1 meningiomas. Targeted sequencing of meningioma-relevant genes was performed to determine the molecular alterations in PMs.

RESULTS

PMs accounted for 1.34% of all meningiomas. Clinically, spinal location (p < 0.001) and female predominance (p < 0.001) were statistically significant in PMs when compared with the other grade 1 subtypes. Radiologically, calcification was frequently found in PMs (88.24%). Genetically, NF2 was the most frequently mutated gene in PMs (59.7%), followed by TRAF7 and AKT1. Ten patients experienced recurrence during the long-term follow-up. Multivariate analysis demonstrated that age (p = 0.009), extent of resection (p < 0.001), Ki-67 index (p = 0.007), and NF2 status (p < 0.001) were independent prognostic factors in the cohort of PMs. Interestingly, NF2 mutation was detected in all (48/48) spinal PMs (SPMs) but in only 38.46% (35/91) of cranial PMs (CPMs), revealing a significant difference (p < 0.001). The mean Ki-67 index (p = 0.044) and proportion of PMs with PR-positive expression (p = 0.048) were significantly higher in SPMs than in CPMs. The frequent NF2 mutations are associated with spinal location predominance and worse PFS in PMs.

CONCLUSIONS

Female sex and spinal location predominance were statistically significant in PMs. NF2 mutation was an independent predictor for worse PFS of PMs. Of note, NF2 mutation was detected in all SPMs but in only 38.46% of CPMs, revealing a significant difference.

摘要

目的

砂粒体型脑膜瘤(PMs)是脑膜瘤的一种罕见组织学亚型,但在脊髓脑膜瘤中较为常见。作者旨在分析 PMs 的发病率、临床特征、分子改变、长期预后和预后因素。

方法

本研究共纳入 151 例 PMs 患者。分析 PMs 的临床特征、分子改变和无进展生存期(PFS)。比较 PMs 与其他 WHO 1 级脑膜瘤的临床特征。对脑膜瘤相关基因进行靶向测序,以确定 PMs 的分子改变。

结果

PMs 占所有脑膜瘤的 1.34%。临床特征上,与其他 1 级亚型相比,PMs 中脊髓位置(p<0.001)和女性优势(p<0.001)具有统计学意义。影像学上,PMs 常伴有钙化(88.24%)。遗传学上,NF2 是 PMs 中最常突变的基因(59.7%),其次是 TRAF7 和 AKT1。10 例患者在长期随访中复发。多因素分析显示,年龄(p=0.009)、切除程度(p<0.001)、Ki-67 指数(p=0.007)和 NF2 状态(p<0.001)是 PMs 队列中的独立预后因素。有趣的是,NF2 突变在所有(48/48)脊髓 PMs(SPMs)中均被检测到,但在仅 38.46%(35/91)颅脊 PMs(CPMs)中被检测到,差异显著(p<0.001)。SPMs 的平均 Ki-67 指数(p=0.044)和 PMs 中 PR 阳性表达的比例(p=0.048)均显著高于 CPMs。NF2 突变的频繁发生与脊髓位置优势和 PMs 的 PFS 恶化有关。

结论

女性和脊髓位置优势在 PMs 中具有统计学意义。NF2 突变是 PMs PFS 不良的独立预测因子。值得注意的是,NF2 突变在所有 SPMs 中均被检测到,但在仅 38.46%的 CPMs 中被检测到,差异显著。

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