title: CD133 identifies perivascular niches in grade II-IV astrocytomas.
abstract: The aim of the present study was to investigate the localization and distribution of the putative brain tumour stem cell marker CD133 in formalin fixed paraffin embedded astrocytomas. A retrospective analysis of 114 grade II, III and IV astrocytomas was undertaken. The immunohistochemical expression of CD133 in paraffin sections was analysed using morphometry. In all grades, CD133 was expressed on tumour and endothelial cells. Tumour cells were found in perivascular niches, as dispersed single cells and in pseudopalisade formations around necrosis. There was no correlation between the mean volume fraction of CD133(+) niches and all CD133(+) tumour cells and tumour grade. However, the volume fraction of CD133(+) blood vessels increased significantly from 0.4% in diffuse astrocytomas to 2.2% in glioblastomas. Neither of them was related to patient survival. Double immunofluorescence stainings showed that the CD133(+) niches both contained CD133(+) cells with and without co-expression of the intermediate filament protein marker nestin, and only few CD133(+)/MIB-1(+) proliferating cells were found. In conclusion, a CD133(+) perivascular stem cell-like entity exists in astrocytomas. CD133(+) tumour vessels may play an important role in a brain tumour stem cell context, while CD133 alone does not appear to be a specific tumour stem cell marker related to patient survival.
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark. karina.christensen@ouh.regionsyddanmark.dk
authors.forename: Karina
authors.initials: K
authors.lastname: Christensen
authors.forename: Henrik D
authors.initials: HD
authors.lastname: Schrøder
authors.forename: Bjarne W
authors.initials: BW
authors.lastname: Kristensen
mesh_terms: D000071916:AC133 Antigen; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007211:Indoles; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010455:Peptides / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D055815:Young Adult
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D007211:Indoles; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides; C007293:DAPI; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases