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

  • Magnetic Resonance
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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.

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Abbreviations

2-D-HG:

(D)-2-Hydroxyglutarate

ATRX:

Alpha thalassemia mental retardation X-linked gene

Cho:

Choline

Cr:

Creatine

GBM:

Glioblastoma

Glx:

Glutamate and glutamine

HGG:

High-grade gliomas

IDH1:

Isocitrate dehydrogenase gene 1

IRR:

Inter-rater reliability analysis

Lac:

Lactate

Lip:

Mobile lipids

mIno:

Myo-inositol

MRSI:

3D chemical shift imaging sequence

mut:

Mutated

NAA:

N-Acetyl aspartate

NAWM:

Normal-appearing white matter

wt:

Wild-type

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Acknowledgments

We would like to thank Mr. David González García, Ms. Evelyn Teruel Sánchez, Mr. Jonathan Monge Ivars, Ms. Sonia Álvarez Bernabéu, and Mr. Enrique García Rodriguez for their outstanding work during the acquisition of the studies; Estefania Rojas Calvente for her support in the histopathology analyses; Mr. Jorge Esteban Jarabo for his invaluable help and advice on the process of writing and improving the manuscript readability; and Mr. Javier Sánchez González (Philips, Spain) for his advice and technical support during the study. We would also like to show our gratitude to the anonymous reviewers who provided insight and expertise that greatly improved the manuscript.

Funding

This work was supported in part by the Centro para el Desarrollo Tecnológico Industrial (CDTI) under the project BRAIM (IDI- 20130020).

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Authors and Affiliations

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

    Ángela Bernabéu-Sanz

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

    María Fuentes-Baile

  3. Pathology Department, Hospital General Universitario de Alicante, ISABIAL, Alicante, Spain

    Cristina Alenda

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  1. Ángela Bernabéu-Sanz
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  3. Cristina Alenda
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Correspondence to Ángela Bernabéu-Sanz.

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Bernabéu-Sanz, Á., Fuentes-Baile, M. & Alenda, C. Main genetic differences in high-grade gliomas may present different MR imaging and MR spectroscopy correlates. Eur Radiol 31, 749–763 (2021). https://doi.org/10.1007/s00330-020-07138-4

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