title: Expression of the stem cell marker CD133 in recurrent glioblastoma and its value for prognosis.
abstract: BACKGROUND
  Experimental data suggest that glioblastoma cells expressing the stem cell marker CD133 play a major role in radiochemoresistance and tumor aggressiveness. To date, however, there is no clinical evidence that the fraction of CD133-positive cells in glioblastoma that recurs after radiochemotherapy may be relevant for prognosis.
  
  
  METHODS
  The authors used immunohistochemistry to assess CD133 expression in 37 paired glioblastoma samples, including 1 primary tumor sample and 1 recurrent tumor sample, after patients received adjuvant radiochemotherapy. To assess the actual composition of the CD133-positive glioblastoma cell population, fluorescence-associated cell sorting (FACS) analysis was used to sort CD133-positive/CD45-negative cells that were assayed for tumor-specific chromosomal aberrations using interphase fluorescence in situ hybridization. To rule out endothelial precursor cells, CD133-positive fractions also were assayed with anti-CD34 by FACS.
  
  
  RESULTS
  In recurrent glioblastomas, the percentage of CD133-positive cells was increased by 4.6-fold compared with the percentage in primary glioblastomas, although, in some tumors, it increased up to 10-fold and 20-fold. Unexpectedly, the increase in CD133 expression was associated significantly with longer survival after tumor recurrence. An analysis of tumor-specific chromosomal aberrations and in vivo studies revealed that the CD133-positive cell compartment of recurrent glioblastoma was composed of both cancer stem cells and nontumor neural stem cells. The latter cells represented from 20% to 60% of the CD133-positive cell population, and their relative percentage favorably affected the survival of patients with recurrent glioblastoma. Endothelial CD133-positive/CD34-positive precursors did not contribute to the CD133-positive cell population.
  
  
  CONCLUSIONS
  The authors hypothesized that, similar to the phenomenon described in glioblastoma models, neural stem/progenitor cells that are recruited by the tumor from surrounding brain may exert an antitumorigenic effect.
authors.affiliation: Institute of Neurosurgery, Catholic University School of Medicine, Rome, Italy. pallini@rm.unicatt.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Pallini
authors.forename: Lucia
authors.initials: L
authors.lastname: Ricci-Vitiani
authors.forename: Nicola
authors.initials: N
authors.lastname: Montano
authors.forename: Cristiana
authors.initials: C
authors.lastname: Mollinari
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffoni
authors.forename: Tonia
authors.initials: T
authors.lastname: Cenci
authors.forename: Francesco
authors.initials: F
authors.lastname: Pierconti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011379:Prognosis; D012008:Recurrence
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides