Article
Unfavourable prognostic influence of IDH1 mutations in WHO Grade II astrocytomas turns into favourable predictive impact after malignant transformation
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Published: | April 28, 2011 |
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Objective: The favourable impact of isocitrate dehydrogenases 1 (IDH1) mutations is well documented for malignant gliomas. Its influence on WHO grade II gliomas, however, remains unclear.
Methods: IDH1 codon 132 pyrosequencing was performed in a mainly surgically treated series of 159 adult patients (1991–1998) harbouring WHO grade II gliomas (24 oligoastrocytomas). In addition MGMT promoter methylation was assessed by methylation-specific polymerase-chain reaction (MSP) and bisulfite sequencing. TP53 mutations were determined by sequencing analysis. Endpoints were overall survival (OS), progression-free survival (PFS), time to malignant transformation and post-recurrence survival (PRS).
Results: IDH1 mutations, TP53 mutations, and methylated MGMT promoters were seen in 77.9%, 45.9%, and 82.8% of analyzed tumors, respectively. The IDH1 mutation was strongly associated with both TP53 mutation and MGMT promoter methylation (p<0.001). IDH1 mutations correlated with shortened PFS (median 49 vs 84 months; p=0.003) but prolonged PRS after malignant transformation and subsequently applied radiotherapy (median: 24 vs. 8 months; p=0.01). A similar pattern of influence was seen for MGMT promoter methylation: methylated tumors did worse in terms of PFS and time to malignant transformation (p>0.05). In contrast, PRS was improved after malignant transformation (p<0.05). This analysis, however, was limited by a low number of unmethylated tumors. Conversely, TP53 mutations were stringently associated with a worse prognosis throughout the course of the disease.
Conclusions: The IDH1 mutation exhibits Janus Head-like properties: Its unfavourable prognostic influence on PFS turns into a favourable predictive impact after malignant transformation. A similar pattern of influence might exist for MGMT methylation.