gms | German Medical Science

Introduction: Microenvironment exerts its effects at the most on perivascular and perinecrotic niches where glioblastoma stem cells (GSCs) are believed to be located in glioblastoma multiforme (GBM). The histological definition of the niches is not univocal. The perinecrotic ones develop around circumscribed necroses that originate from hypoxia and GSCs from the activation of HIF-1/2.

Objectives: An alternative interpretation to the occurrence of GSCs in perinecrotic position is that they represent the residue of GSCs which populated the hyperproliferating area where necrosis develops surviving it.

Materials and Methods: In a series of 20 GBMs the proliferating zones were studied histologically, immunohistochemically and by immunofluorescence by stemness (Nestin, SOX2, REST, CD133, Musashi.1 and Oct4) and differentiation (GFAP, βIII-tubulin, GalC) antigens and by HIF-1/2.

Results: Hyperproliferating areas are rich in stemness and poor in differentiations antigens. With the development of necrosis, due to the imbalance between the proliferation capacity of tumor and endothelial cells, this appears as surrounded by HIF-1-, Nestin- and SOX2-positive cells.

Conclusion: This is an alternative interpretation to the generally accepted perinecrotic niche formation in GBMs. It is based on the understanding of GSCs as a functional status due to the acquisition of stemness properties by the dedifferentiation of the most malignant tumor cells.