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高级别胶质瘤的主要遗传差异可能表现出不同的磁共振成像和磁共振波谱学相关性。

Main genetic differences in high-grade gliomas may present different MR imaging and MR spectroscopy correlates.

机构信息

Magnetic Resonance Department, Hospital General Universitario de Alicante, Inscanner SL, C/ Pintor Baeza, 11, 03010, Alicante, Spain.

Research Laboratory, Hospital General Universitario de Alicante, ISABIAL, Alicante, Spain.

出版信息

Eur Radiol. 2021 Feb;31(2):749-763. doi: 10.1007/s00330-020-07138-4. Epub 2020 Sep 1.

Abstract

OBJECTIVE

To assess whether the main genetic differences observed in high-grade gliomas (HGG) will present different MR imaging and MR spectroscopy correlates that could be used to better characterize lesions in the clinical setting.

METHODS

Seventy-nine patients with histologically confirmed HGG were recruited. Immunohistochemistry analyses for isocitrate dehydrogenase gene 1 (IDH1), alpha thalassemia mental retardation X-linked gene (ATRX), Ki-67, and p53 protein expression were performed. Tumour radiological features were examined on MR images. Metabolic profile and infiltrative pattern were assessed with MR spectroscopy. MR features were analysed to identify imaging-molecular associations. The Kaplan-Meier method and the Cox regression model were used to identify survival prognostic factors.

RESULTS

In total, 17.7% of the lesions were IDH1-mutated, 8.9% presented ATRX-mutated, 70.9% presented p53 unexpressed, and 22.8% had Ki-67 > 5%. IDH1 wild-type tumours had higher levels of mobile lipids (p = 0.001). The tumour-infiltrative pattern was higher in HGG with unexpressed p53 (p = 0.009). Mutated ATRX tumours presented higher levels of glutamate and glutamine (Glx) (p = 0.001). An association was observed between Glx tumour levels (p = 0.038) and Ki-67 expression (p = 0.008) with the infiltrative pattern. Survival analyses identified IDH1 status, age, and tumour choline levels as independent predictors of prognostic significance.

CONCLUSIONS

Our results suggest that IDH1-wt tumours are more necrotic than IDH1-mut. And that the presence of an infiltrative pattern in HGG is associated with loss of p53 expression, Ki-67 index, and Glx levels. Finally, tumour choline levels could be used as a predictive factor in survival in addition to the IDH1 status to provide a more accurate prediction of survival in HGG patients.

KEY POINTS

• IDH1-wt tumours present higher levels of mobile lipids than IDH1-mut. • Mutated ATRX tumours exhibit higher levels of glutamate and glutamine. • Loss of p53 expression, Ki-67 expression, and glutamate and glutamine levels may contribute to the presence of an infiltrative pattern in HGG.

摘要

目的

评估高级别胶质瘤(HGG)中观察到的主要遗传差异是否会呈现出不同的磁共振成像(MR)和磁共振波谱(MRS)相关性,以便在临床环境中更好地对病变进行特征描述。

方法

共招募了 79 名经组织学证实的 HGG 患者。进行了异柠檬酸脱氢酶基因 1(IDH1)、α-地中海贫血智力迟钝 X 连锁基因(ATRX)、Ki-67 和 p53 蛋白表达的免疫组织化学分析。在 MR 图像上检查肿瘤的放射学特征。使用 MRS 评估代谢谱和浸润模式。分析 MR 特征以确定成像-分子关联。采用 Kaplan-Meier 法和 Cox 回归模型确定生存预后因素。

结果

共发现 17.7%的病变为 IDH1 突变型,8.9%为 ATRX 突变型,70.9%为 p53 无表达型,22.8%为 Ki-67>5%。IDH1 野生型肿瘤中移动脂质水平更高(p=0.001)。p53 无表达的 HGG 中肿瘤浸润模式更高(p=0.009)。突变 ATRX 肿瘤的谷氨酸和谷氨酰胺(Glx)水平更高(p=0.001)。观察到 Glx 肿瘤水平(p=0.038)与 Ki-67 表达(p=0.008)与浸润模式之间存在关联。生存分析确定 IDH1 状态、年龄和肿瘤胆碱水平为独立的预后预测因素。

结论

我们的研究结果表明,IDH1-wt 肿瘤比 IDH1-mut 肿瘤更具坏死性。并且,HGG 中浸润模式的存在与 p53 表达缺失、Ki-67 指数和 Glx 水平有关。最后,除 IDH1 状态外,肿瘤胆碱水平可作为生存的预测因素,为 HGG 患者的生存提供更准确的预测。

关键点

  1. IDH1-wt 肿瘤中移动脂质水平高于 IDH1-mut。

  2. 突变 ATRX 肿瘤中谷氨酸和谷氨酰胺水平较高。

  3. p53 表达缺失、Ki-67 表达、谷氨酸和谷氨酰胺水平的缺失可能导致 HGG 中浸润模式的存在。

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