Artikel
Does the spatial relationship of primary glioblastoma to the subventricular zone impact on neural stem cell marker expression and survival?
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Autoren
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C. Dictus
- Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
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S. Friauf
- Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
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N.A. Valous
- Tissue Imaging and Analysis Center, Institut für Medizinische Biometrie und Informatik, Universität Heidelberg
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B. Muerle
- Zentralabteilung für Diagnostische und Interventionelle Radiologie, Theresienkrankenhaus, Mannheim
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C.H. Herold-Mende
- Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
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A.W. Unterberg
- Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
| Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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Objective: There is an ongoing debate whether neural stem cells residing in the subventricular zone (SVZ), the predominant neurogenic region of the adult brain, give rise to glioblastomas (GBM). A recent publication by Lim et al. (Neuro-Oncol 9(4), 2007) showed that the spatial relationship of GBM to the SVZ predicts a multifocal and invasive phenotype. We therefore sought to determine whether vicinity to SVZ impacts on neural stem cell marker expression and survival in patients with primary GBM.
Methods: Cryostate tissue sections of 106 primary GBM patients and 16 corresponding recurrent tumours were stained for six major neural stem cell markers (CD133, ALDH1A, GFAP delta, FABP7, SOX-2, SSEA-1). After digitalization of slides, quantification of expression was carried out using colour deconvolution. Respective preoperative MRI scans were reviewed and tumours were classified according to Lim et al. (2007): (I) GBM contacting SVZ and infiltrating cortex, (Il) GBM contacting SVZ but not involving cortex, (III) GBM not contacting SVZ but infiltrating cortex, (IV) GBM neither contacting SVZ nor infiltrating cortex. Clinical data were available for all patients analyzed.
Results: GBM localization was mainly assigned to groups I (31.1%) and III (38.7%) and multifocal tumour growth was restricted to these two groups. Analysis of the whole patient sample failed to demonstrate a correlation between GBM localization and patient survival; however, analyzing the subgroup of completely resected patients (30.2%), a significant survival benefit (OS: p = 0.04; PFS: p = 0.03) was seen for GBMs contacting the SVZ (I, II). Noteworthy, in tumours adjacent to the SVZ (I, II), a significant correlation to stem cell marker expression was only found for CD133 (p = 0.006) whereas GBMs with subcortical localization (II, IV) demonstrated a significant overexpression of FABP7 (p = 0.03). Interestingly, 53–87% of the recurrent tumour tissues analyzed displayed enhanced stem cell marker expression compared to the respective primary tumours.
Conclusions: These preliminary findings mitigate the hypothesis that GBMs contacting the SVZ are enriched in (potentially tumourigenic) neural stem cells that impact on patient survival. However, in these tumours a complete resection seems to exert an exceptionally prognostic benefit. Multivariate analysis is currently under way to underline the results.
