Objective: With the objective of investigating the utility of CXCR4, a chemokine receptor known to mediate glioma cell invasiveness, as a molecular marker for peritumoral disease extent in high-grade gliomas, we sought to characterize the expression profile of CXCR4 in a large panel of tumor samples and determine whether CXCR4 expression levels within glioblastoma multiforme might correlate with radiological evidence of a more extensive disease process.
Methods: Freshly resected tumor tissue samples were processed for immunohistochemical and quantitative polymerase chain reaction analyses to identify and quantify expression levels of CXCR4 and its corresponding ligand CXCL12. T1 postcontrast and T2-weighted magnetic resonance imaging brain scans were used to generate voxel signal intensity histograms that were quantitatively analyzed to determine the extent and intensity of peritumoral signal abnormality as a marker of disseminated disease in the brain.
Results: CXCR4 expression was markedly elevated in Grade III and IV tumors compared with Grade II gliomas. Significantly, when patients with glioblastoma multiforme were segregated into two groups based on CXCR4 expression level, we observed a statistically significant increase in the intensity and extent of peritumoral magnetic resonance imaging signal abnormalities associated with CXCR4 high-expressing gliomas.
Conclusion: Our data confirm that high-grade gliomas robustly express CXCR4 and demonstrate a correlative relationship between expression levels of the CXCR4 receptor and the magnetic resonance imaging-based finding of a diffuse and more extensive disease process in the brain. CXCR4 expression status may, therefore, prove useful as a marker of disseminated disease in patients with glioblastoma multiforme.