IDH1 R132H Mutation Is Accompanied with Malignant Progression of Paired Primary-Recurrent Astrocytic Tumours.

Abstract

IDH1 R132H mutation is an important marker of survival in patients with gliomas. Although there are many changes of genes in tumour malignant progression, IDH1 R132H mutation status in glioma progression remained unclear. Here, an in-depth characterization of IDH1 R132H mutations were assessed by immunohistochemistry in 55 paired primary-recurrent astrocytomas tissues, including 5 paired primary pilocytic astrocytoma (pPA, WHO grade I), 35 paired primary low grade astrocytoma (pLGA, WHO grade II and III) and 15 paired primary high grade astrocytoma (pHGA/ Glioblastoma, WHO grade IV). Meanwhile, the DNA was isolated from paired samples, and PCR amplification was used for IDH1 exon4 sequencing. Nonparametric test, KM and Cox models were used to examine the statistical difference and survival function. We found that the percent of IDH1 R132H mutation was 68.6% (24/35) in pLGA group, but no IDH1 mutation was found in pPA and pHGA groups. Meanwhile, the results from immunohistochemistry and DNA sequencing showed that, compared with primary astrocytoma, there was no change of IDH1 status in recurrent astrocytoma whatever tumour pathological grade raise or indolent. The pPA group has the longest recurrence-free period (RFP) and overall survival (OS) in three groups (p<0.01), while the pHGA group has the shortest ones (p<0.01). In pLGA group, the IDH1 R132H mutation subgroup has longer RFP than IDH1 wild type subgroup (p<0.01), but the OS has no statistical difference between two subgroups (p>0.6). Additionally, IDH1 R132H mutation independently predicted a long RFP in patients with pLGA (HR 1.073, 95% CI 0.151-0.775, p<0.01).