Background: Glioblastomas are highly angiogenic tumours that overexpress vascular endothelial growth factor (VEGF). However, the anti-VEGF antibody bevacizumab has not improved overall survival time for patients. Vasculogenic mimicry (VM) is the ability of tumour cells to form functional blood vessels that lack an endothelial lining and may compensate for insufficient angiogenesis. VM has been reported in primary glioblastoma tissue but has not been investigated in recurrent tumours. We aimed to assess the extent of VM formation in both primary and recurrent glioblastoma and determine whether the presence of VM is associated with patient survival.
Methods: Thirty-five matched pairs of primary and recurrent formalin-fixed paraffin-embedded glioblastoma tissue were immunohistochemically labelled for the endothelial cell marker CD34 and stained with periodic acid-Schiff (PAS). Vascular structures were categorised as endothelial vessels (CD34+/PAS+) or VM (CD34-/PAS+). Vessels were counted in ten randomly selected regions within each tumour and a vessel density/mm2 for each vessel category was determined. Data are expressed as median values.
Results: Endothelial vessels accounted for the majority of blood vessels in both primary and recurrent tumours. There was a significant decrease in endothelial vessels in recurrent (41.34 vessels/mm2) compared to primary (86.98 vessels/mm2) glioblastomas (p <0.001). VM was observed in 15/35 primary tumours (42.86%) and 10/35 recurrent tumours (28.57%). VM vessels accounted for a small proportion of the tumour vasculature and did not differ in density between primary and recurrent tumours (p = 0.266). Kaplan-Meier analyses with log rank tests indicated that VM- tumours had longer median overall survival time than VM+ tumours, regardless of whether VM status was determined based on the primary or recurrent tumour. However, there was no significant difference in overall survival distributions (primary χ2(1) = 0.381, p = 0.537; recurrent χ2(1) = 3.552, p = 0.059). Cases that were VM- at recurrence had significantly longer post-progression survival than those that were VM+ (χ2(1) = 4.830, p = 0.028).
Conclusions: Categorical stratification of tumours into VM+ and VM- groups indicated that the presence of VM at recurrence is associated with shorter post-progression survival. However, VM density was very low in both primary and recurrent glioblastoma, and the extent to which VM contributes functionally to the tumour vasculature and its potential as a treatment target require further investigation.