Table 1.
Summary of the features of the peritumoral brain zone
| Approach | Technique | Characteristics of the PBZ | References |
|---|---|---|---|
| Radiology-MRI | T1 | • No contrast enhancement | |
| T2 FLAIR | • Hypersignal | ||
| ADC | • Intensity of the signal correlated to tumor cell infiltration | 27–30 | |
| DTI | • Inverse correlation between the fractional anisotropy and tumoral infiltration of the PBZ | 34–37 | |
| DCE | • Volume transfer coefficient (ktrans) is correlated with tumoral infiltration and histological grading | 23,31 | |
| • Extracellular volume (Ve) and capillary transit time (Tc) are correlated with molecular markers of hypoxia and overall patient survival | 32,33 | ||
| Cell biology | Tumor cells | • Tumor cells found in the PBZ differ from those in the corresponding tumor mass | 25,39–41 |
| • Some, but not all tumor clones, migrate away from the tumor core into the PBZ | 23 | ||
| • High proliferation and invasiveness | 25,40 | ||
| • Different response to drug and radiation challenge in vitro | 25 | ||
| • Migrate along the same route of neural stem cells and share numerous traits with them | 38 | ||
| Reactive astrocytes | • Promote tumor growth and survival by secreting cytokines | 44–46 | |
| • May be involved in immune reactions against the tumor | 49 | ||
| Inflammatory cells | • Macrophage density proportional to histological grade and vascular density | 52 | |
| • Tumor-associated macrophages and their activation state have prognostic value | 53–55 | ||
| GASCs | • Phenotype close to CAFs | 15,16 | |
| • Angiogenic and tumor-promoting properties in vitro and in vivo, depending on the GASC subtype | 15,16,24 | ||
| Molecular biology | Immunohistochemistry | • Strong expression of adenosine A1 receptor and STAT1, conferring a neuroprotective effect | 62–64 |
| • High concentrations of copper and zinc | 62 | ||
| • Expression of CD105, ERKs & JNK, associated with poor prognosis | 59–61 | ||
| • Expression of VEGF associated with poor progression-free survival | 32 | ||
| Genomics | • Presence of some but not all genomic alterations in the nearby tumor zone | ||
| • Loss/partial loss of chromosome 10, polysomy of chromosome 7 and focal amplification of EGFR | 23 | ||
| Transcriptomics | • PBZ has a proneural or neural profile, irrespective of the adjacent GB subtype | 10–12 | |
| • Interpatient variability, similar to that observed in the corresponding TZ | 10–12 | ||
| • Intratumoral gradient of gene expression from the tumor core to the PBZ | 10–12 | ||
| • Overexpression of genes associated with growth and proliferation and cell motility/adhesion and underexpression of those involved in neurogenesis | 67 | ||
| • Nonneoplastic cells in the PBZ and the GB subtype may influence the molecular profile of the PBZ | 68 | ||
| • MicroRNA deregulation in GB and adjacent brain | 69 | ||
| Proteomics | • Large interpatient variability complicates the identification of protein markers of the PBZ | 18 |
Abbreviations: ADC, apparent diffusion coefficient; CAFs, cancer-associated fibroblasts; DCE, dynamic contrast enhancement; DTI, diffusion tensor imaging; ERKS, extracellular signal-regulated kinases; FLAIR, fluid-attenuated inversion recovery; GASC, glioblastoma-associated stromal cell; GB, glioblastoma; JNK, c-Jun NH2 terminal kinases; PBZ, peritumoral brain zone.