Study of stem cell marker nestin and its correlation with vascular endothelial growth factor and microvascular density in ependymomas

Background: Ependymomas are relatively rare glial tumours, whose pathogenesis is not well elucidated. They are enigmatic tumours that show site-specific differences in their biological behaviour. Recent studies have hypothesized that ependymoma cancer stem cells (CSCs) are derived from radial glia and express stem cell markers such as nestin, which is associated with a poor prognosis. CSCs reside in 'vascular niches', where endothelial cells and molecular signals like vascular endothelial growth factor (VEGF) play an important role in their survival. Studies analysing VEGF expression in ependymomas showed that ependymal vascular proliferation is less sensitive to induction by VEGF, questioning the possible beneficial effect of anti-VEGF therapy in ependymomas. We aimed to study nestin and VEGF immunoexpression in ependymomas, correlate them with clinicopathological parameters and reveal a role for VEGF in ependymomas that extends beyond the context of tumour angiogenesis. Methods: We analysed 126 cases of ependymomas of different grades and locations for nestin and VEGF immunoexpression. Endothelial cells were labelled with CD34. Vascular patterns and microvascular density was determined. Results: Nestin and VEGF expression in tumour cells were more frequent in supratentorial tumours [89% (33/37) and 65% (24/37) respectively], and were associated with a significantly poor progression-free survival (PFS). VEGF expression did not reveal any correlation with necrosis or bizarre vascular patterns. Conclusions: Supratentorial location is an independent predictor of a poor PFS. Significant coexpression of nestin and VEGF suggests that latter possibly augments stem cell survival. Thus, anti-VEGF therapy may be a good option in future for nestin immunopositive ependymomas.