IDH1 mutations in grade II astrocytomas are associated with unfavorable progression‐free survival and prolonged postrecurrence survival

Abstract

BACKGROUND:The favorable prognostic impact of mutations in the IDH1 gene is well documented for malignant gliomas; its influence on World Health Organization (WHO) grade II astrocytomas, however, is still under debate. METHODS: A previously published database of 127 predominantly surgically treated patients harboring WHO grade II astrocytomas was revisited. Patients were screened for TP53 mutations (sequencing analysis), IDH1 mutations (pyrosequencing), and MGMT promoter methylation (methylation-specific polymerase chain reaction and bisulfite sequencing). Endpoints were overall survival, progression-free survival (PFS), time to malignant transformation, and postrecurrence survival. Radiotherapy was usually withheld until tumor progression/malignant transformation occurred. RESULTS: IDH1 mutations, TP53 mutations, and methylated MGMT promoters were seen in 78.1%, 51.2%, and 80.0% of the analyzed tumors, respectively. IDH1 mutations, which were significantly associated with TP53 mutations and/or MGMT promoter methylation (P < .001), resulted in shortened PFS (median, 47 vs 84 months; P ¼ .004); postrecurrence survival, however, was significantly increased in those patients undergoing malignant transformation (median, 49 vs 13.5 months; P ¼ .006). Overall survival was not affected by IDH1. A similar pattern of influence was seen for MGMT promoter methylation. Methylated tumors did significantly worse (better) in terms of PFS (postrecurrence survival); a low number of unmethylated tumors, however, limited the power of this analysis. Conversely, TP53 mutations were stringently associated with a worse prognosis throughout the course of the disease. CONCLUSIONS: IDH1 mutations are associated with a Janus headlike phenomenon; unfavorable prognostic influence on PFS turns into favorable impact on postrecurrence survival. A similar pattern of influence might exist for MGMT methylation.

IDH Mutation and Neuroglial Developmental Features Define Clinically Distinct Subclasses of Lower Grade Diffuse Astrocytic Glioma

“…In addition, IDH mutation in diffuse astrocytic gliomas correlated with a marked survival benefit that remained even after WHO grade stratification. While this finding is consistent with multiple published reports on WHO II, III, and IV gliomas (5,6,11), other large studies have failed to identify any increase in overall survival associated with IDH mutation specifically in WHO II astrocytomas (39,40). While the precise reasons underlying this discrepancy within the literature are unclear, differences in sample cohorts with regard to histopathologic inclusion/exclusion criteria and patient management may contribute.…”

Potential Utility of Visually AcceSAble Rembrandt Images Assessment in Brain Astrocytoma Grading

“…For example, mutations of the gene encoding isocitrate dehydrogenase 1 are very common in low-grade astrocytomas, oligodendrogliomas, and secondary glioblastomas but very rare in de novo glioblastoma. 20,21 In addition to mutations of isocitrate dehydrogenase 1, low-grade astrocytomas usually have TP53 mutation, whereas oligodendrogliomas typically show 1p/19q loss. 21 Comparing with advanced MRI techniques and genetic characteristics, the VASARI MRI has its own convenience.…”

“…20,21 In addition to mutations of isocitrate dehydrogenase 1, low-grade astrocytomas usually have TP53 mutation, whereas oligodendrogliomas typically show 1p/19q loss. 21 Comparing with advanced MRI techniques and genetic characteristics, the VASARI MRI has its own convenience. Considering the advantages and limitations, we suggest combining advanced MRI and genetic characteristics with VASARI MRI, which could help in better understanding of the tumor behavior and tumor grading.…”

IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO

“…The identification of IDH mutations in the majority of astrocytomas [2, 7, 21, 25] and concurrent analyses revealed that among AA III WHO2007 the presence of these mutations was associated with a significant better clinical course [6, 17, 23], an observation not observed for A II WHO2007 [1, 20]. Numerous studies indicate the possibility that worse outcome of AA III WHO2007 compared to A II WHO2007 is strongly influenced by the inclusion of cases that indeed molecularly represent glioblastoma (GBM).…”