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  • I-FISH and IDH mutation analysis - a valuable prognostic factor in diffuse astrocytomas

    Final Number:
    1400

    Authors:
    Filip Kramar MD; Zuzana Zemanova; Libuse Lizcova PhD; David Netuka MD, PhD; Vladimir Benes MD, PhD; Kyra Michalova PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2013 Annual Meeting

    Introduction: Affected patients with difuse astrocytoma have a rather poor prognosis. Non-random chromosomal abberations influence the prognosis and overall survival (OS) of these patients.

    Methods: The aim of study was fluorescence in-situ hybridisation (FISH) analysis of diffuse astrocytoma tissue samples, correlation with morphological and clinical data and statistical analysis of achieved results. Tissue samples gained during neurosurgical procedure were sent for histological analysis and FISH analysis. Centromeric and probes of selected tumor-suppressor and oncogenes were used: TP53, CDKN2A, RB1, EGFR, chromosome 7, 9, 10, 17. FISH data were correlated with clinical data and validated by Kaplan-Meier analysis and Cox model. In selected patients IDH1/2 status by MLPA was later analyzed.

    Results: Since 2004 to 2010 37 patients underwent surgical procedure in our series, 15 patients are still alive, median OS achieved 67,8 months. FISH analysis was performed in all patients: Monosomy 10 was detected 4x, EGFR amplification 2x, trisomy 7 1x, CDKN2A deletion 2x, RB1 deletion 3x, monosomy 13 a 17 1x. Polyploidy was found in 20 samples. Kaplan-Meier analysis revealed that in group of negative FISH (12 patients) median OS was 90 months, in group of polyploidy (13 patients) 67 months, in group of other abberations except polyploidy (12 patients) median OS was only 37 months, data are statistically significant. In Cox model positive finding of other abberation is statistically significant as negative factor for OS, hazard ratio gained 3,8. IDH1/2 status was revealed in subgroup of 14 patients, IDH1 mutation was found in 12 patients, in this subgroup median OS was 97,1 months.

    Conclusions: In diffuse astrocytomas FISH analysis is relevant tool to predict patients prognosis. If I-FISH reveals chromosomal abberation, patient should be followed as high grade glioma patient. IDH1 mutation seems to be positive prognostic marker in patients with diffuse astrocytoma. Supported by IGA MZ13212

    Patient Care: the follow-up procedure can be changed according to results of genetic profile of a tumor

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of I-FISH analysis and IDH1/2 status 2) Discuss the importance of genetic profiling of glial tumors and possibility to stratify the patients into groups of different risk of tumor upgrading and progression 3) Identify a group of patients with higher risk of tumor upgrading

    References:

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