ИСТИНА

Glioblastoma multiforme (GBM) is an heterogeneous tumor for the histological aspect, aggressiveness, genetic expression and regressive events. Heterogeneity assessment with neuro-imaging can be of help not only for diagnosis, but also for therapies because it gives information about the tumor capacity to reproduce, to recur and to resist therapies. To know the target volume for radiotherapy is important, but also the biological significance of imaging aspects. In particular; two points deserve special concern: the extension of tumor infiltrating area and where cancer stem cells (CSCs) are located or generated.in the tumor. rT1C, rFSE, rFLAlR, DSC (rCBV, H, PSR, RF), DWI (rADC, rFA), Spectroscopy (CNl) and PET imaging were compared with histopathology, immunohistochemistry and genetics of enhancing and non enhancing areas removed by surgical navigation workstation. The capacity to develop CSCs of each removed area was assessed by the neurosphere assay. Neurospheres and adherent cells were characterized by growth rate, clonogenicity, genetics and by expression of stemness or differentiation antigens, also by confocal microscopy.. It was observed that imaging parameters corresponded to different histopathologic aspects in various combination and that cell infiltration could be detected in areas far from the enhancing ring, also in districts apparently normal or edematous only. Very important was the distinction between edema alone or edema plus infiltration. The detection of CSCs was frequent in samples removed from the enhancing ring facing the central necrosis and containing the most malignant tumor phenotype; it progressively decreased until zero moving away from the most malignant district. CSCs are at the top of a hierarchy of tumor cells as for stemness and represent a status that malignant dedifferentiated tumor cells can acquire through a microenvironment with an adequate signalling.