Magnetic Resonance Imaging Derived Biomarkers of IDH Mutation Status and Overall Survival in Grade III Astrocytomas.

Paola Feraco,Antonella Bacci,Salvatore Girlando,Luc Van Den Hauwe,Mattia Barbareschi,Patrizia Ferrazza,Riccardo Pertile,Cesare Gagliardo,Alessio Giuseppe Morganti,Benedetto Petralia

doi:10.3390/diagnostics10040247

Abstract

The evaluation of the isocitrate dehydrogenase (IDH) mutation status in the glioma decision-making process has diagnostic, prognostic and therapeutic implications. The aim of this study was to evaluate whether conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) can noninvasively predict the most common IDH mutational status (R132H) in GIII-astrocytomas and the overall survival (OS). Hence, twenty-two patients (9-F, 13-M) with a histological diagnosis of GIII-astrocytoma and evaluation of IDH-mutation status (12-wild type, 10-mutant) were retrospectively evaluated. Imaging studies were reviewed for the morphological feature and mean ADC values (ADCm). Statistics included a Fisher’s exact test, Student’s t-test, Spearman’s Test and receiver operating characteristic analysis. A p ≤ 0.05 value was considered statistically significant for all the tests. A younger age and a frontal location were more likely related to mutational status. IDH-wild type (Wt) exhibited a slight enhancement (p = 0.039). The ADCm values in IDH-mutant (Mut) patients were higher than those of IDH-Wt patients (p < 0.0004). The value of ADC ≥ 0.99 × 10−3 mm2/s emerged as a “cut-off” to differentiate the mutation state. In the overall group, a positive relationship between the ADCm values and OS was detected (p = 0.003; r = 0.62). Adding quantitative measures of ADC values to conventional MR imaging could be used routinely as a noninvasive marker of specific molecular patterns.

Highlights

In the 2016 World Health Organization (WHO) classification of Tumors of the Central NervousSystem [1], molecular parameters were integrated with histopathology into glioma characterizations to create more biologically homogenous groups
Grades II, III and IV gliomas are divided into isocitrate dehydrogenase (IDH) mutant (Mut) glioma and IDH wild-type (Wt) glioma
The inclusion criteria were: (1) definite histopathologic diagnosis of grade III astrocytoma based on the WHO 2016 classification criteria and (2) cMRI and diffusion weighted imaging (DWI) performed before treatment in the same MR session

Summary

Introduction

In the 2016 World Health Organization (WHO) classification of Tumors of the Central NervousSystem [1], molecular parameters were integrated with histopathology into glioma characterizations to create more biologically homogenous groups. Grades II, III and IV gliomas are divided into isocitrate dehydrogenase (IDH) mutant (Mut) glioma and IDH wild-type (Wt) glioma. An IDH mutation is a distinctive genomic alteration that plays important roles in gliomagenesis and occurs in 70% to 90% of grade II/III gliomas. 2-hydroxyglutarate (2-HG), leading to a slower growth of tumor cells compared to the wild types [2]. The analysis of histopathological specimens through immunohistochemistry and genomic sequence is the gold standard method for detecting IDH mutations in patients with glioma. These methods are invasive, and, due to intratumoral heterogeneity, standard biopsies may lead to an incorrect result. Medical imaging procedures can evaluate the entire tumor in a noninvasive and reproducible way

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