Article
Association of molecular markers with tumor location and subventricular zone involvement in malignant glioma
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Authors
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Yahya Ahmadipour
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Essen, Essen
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Oliver Müller
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Essen, Essen
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Marc Schlamann
- Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie, Universitätsklinikum Essen, Essen
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Zhu Yuan
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Essen, Essen
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Ulrich Sure
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Essen, Essen
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Nicolai El Hindy
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Essen, Essen
| Published: | June 2, 2015 |
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Outline
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Objective: Malignant gliomas (MG) are the most common type of CNS tumors, currently graded by histopathological features. Multiple studies identified important molecular markers like IDH1/2 gene mutations, MGMT promoter methylation and p53 mutations with significant impact on survival. Therefore molecular subtyping rather than histological description of phenotypes is thought to better classify MG. Furthermore, MG are distributed to different cerebral locations sometimes with subventricular zone involvement (SVZ) which represents the origin of cancer stem cells. Hitherto, little is known about the correlation between these molecular markers, tumor location as well as SVZ.
Method: Adult patients (>18 years) with malignant glioma (WHO°III/IV) operated at our institution in 2013 were included in this survey. Preoperative MRI findings like SVZ, tumor location, and infiltration of more than one lobe were analysed. IDH1/2 mutation, MGMT promoter methylation and finally p53 mutation were determined. Statistical analyses were conducted using SPSS version 19.0.
Results: 95 patients were analysed, comprising 59(62.1%) male and 36(37.9%) female patients with a median age of 61.5(32-81) years. 77(81.1%) patients harboured the IDH1/2 wild type, 17 (17.9%) the p53 wild type and 48 (50.5%) patients had no methylation of the MGMT promotor. We found an association between single lobe involvement and IDH1/2 mutation. All multilocular MG, as well as patients suffering from gliomatosis cerebri harboured exclusively the IDH1/2 wildtype (p=0.005). Moreover not a single tumor with infiltration of the SVZ revealed IDH1/2 mutation, but solely the wild type variant (p=0.035). MGMT promotor methylation, and p53 mutation was not associated with SVZ involvement so far. All tumors (n=14, 14.7%) harbouring an oligodendroglial component had a positive MGMT promoter methylation (p=0.04).
Conclusions: Our results confirm previous findings of possible molecular subtypes of histologically graded malignant gliomas. IDH1/2 mutational status seems to influence tumor location and subventricular involvement or vice versa. Infiltration of the subventricular zone, as a potent area of stem cells is known to be associated with a worse prognosis. The same is true for IDH1/2 wild type tumors. Further studies are necessary to reveal the association between IDH1/2 mutational status, subventricular zone involvement and cerebral anatomic location.
