ABSTRACT
Background: The subventricular zone (SVZ) of the human brain is a site of adult stem cell proliferation and a microenvironment for neural stem cells (NSCs). It has been suggested that NSCs in the SVZ are potential cells of origin containing driver mutations of glioblastoma, but their role in the origin of diffuse lower-grade gliomas (dLGGs) is not much studied. Methods: We included 188 patients ≥18 years with IDH-mutated dLGG (WHO grades 2-3) histologically diagnosed between 2007 and 2020. Tissue microarrays of tumor samples for patients between 2007 and 2016 were used for immunodetection of Nestin, SOX2, SOX9, KLF4, NANOG, CD133 cMYC, and Ki67. DNA methylation profile was used for stemness index (mDNAsi). Tumor contact with the SVZ was assessed and the distance was computed. Results: Overall, 70.2% of the dLGG had SVZ contact. Tumors with SVZ contact were larger (102.4 vs 30.9 mL, P < .01), the patients were older (44.3 vs 40.4 years, P = .04) and more often had symptoms related to increased intracranial pressure (31.8% vs 7.1%, P < .01). The expression of SOX2, SOX9, Nestin, and Ki67 showed intersample variability, but no difference was found between tumors with or without SVZ contact, nor with the actual distance to the SVZ. mDNAsi was similar between groups (P = .42). Conclusions: We found no statistical relationship between proximity with the SVZ and mDNAsi or expression of SOX2, SOX9, Nestin, and Ki67 in IDH-mutated dLGG. Our data suggest that the potential impact of SVZ on IDH-mutated dLGG is probably not associated with a more stemness-like tumor profile.
ABSTRACT
BACKGROUND: Glioma is the most common intra-axial tumor, and its location relative to critical areas of the brain is important for treatment decision-making. Studies often report tumor location based on anatomical taxonomy alone since the estimation of eloquent regions requires considerable knowledge of functional neuroanatomy and is, to some degree, a subjective measure. An unbiased and reproducible method to determine tumor location and eloquence is desirable, both for clinical use and for research purposes. OBJECTIVE: To report on a voxel-based method for assessing anatomical distribution and proximity to eloquent regions in diffuse lower-grade gliomas (World Health Organization grades 2 and 3). METHODS: A multi-institutional population-based dataset of adult patients (≥18 years) histologically diagnosed with lower-grade glioma was analyzed. Tumor segmentations were registered to a standardized space where two anatomical atlases were used to perform a voxel-based comparison of the proximity of segmentations to brain regions of traditional clinical interest. RESULTS: Exploring the differences between patients with oligodendrogliomas, isocitrate dehydrogenase (IDH) mutated astrocytomas, and patients with IDH wild-type astrocytomas, we found that the latter were older, more often had lower Karnofsky performance status, and that these tumors were more often found in the proximity of eloquent regions. Eloquent regions are found slightly more frequently in the proximity of IDH-mutated astrocytomas compared to oligodendrogliomas. The regions included in our voxel-based definition of eloquence showed a high degree of association with performing biopsy compared to resection. CONCLUSION: We present a simple, robust, unbiased, and clinically relevant method for assessing tumor location and eloquence in lower-grade gliomas.
