Spatial heterogeneity of malignant molecular markers in glioma revealed by stereotactic biopsy
Caohang Qiu1,2,3,4, Kaixi Wei1,2,3,4,5, Chunhua Wang5
1Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China.
Purpose:
To investigate the spatial distribution of key malignant molecular markers in glioma using MRI-guided stereotactic biopsies for tissue validation.
Materials And Methods:
Thirty-seven patients with newly suspected gliomas underwent preoperative magnetic resonance imaging (MRI) followed by MRI-guided stereotactic biopsy and subsequent open craniotomy. Using preoperative MRI (T2-weighted imaging [T2WI]/fluid-attenuated inversion recovery [FLAIR] and contrast-enhanced T1WI), each tumor was radiologically subdivided into core, middle, and peripheral regions. Representative tissues from these regions were obtained via stereotactic biopsy. Immunohistochemistry (IHC) was performed to detect the expression of Ki67, ZEB1, NOTCH1, and HIF-1α.
Results:
The expression levels of Ki67, ZEB1, NOTCH1, and HIF-1α were positively correlated with increasing glioma grade (Kruskal-Wallis test, all P < 0.05).A significant spatial gradient was observed for Ki67 (P < 0.001), ZEB1 (P < 0.001), HIF-1α (P < 0.001), and NOTCH1 (P = 0.001) expression across the core, middle, and peripheral regions (Friedman test). Post-hoc pairwise comparisons confirmed the most pronounced difference was between the core and periphery for all markers (all P < 0.001).
Conclusions:
The expression of Ki67, ZEB1, NOTCH1, and HIF-1α is closely associated with the malignant grade of gliomas and exhibits a conserved "core-to-periphery" decreasing gradient. The tumor core appears to be the molecular epicenter of aggressive phenotypes. These findings underscore the importance of targeting the radiologic core for diagnostic biopsy to avoid under-grading and suggest that spatial heterogeneity should be considered in therapeutic planning.
