title: Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme.
abstract: OBJECTIVE
  Cancer stem cells (CSC) are thought to represent the population of tumorigenic cells responsible for tumor development. The stem cell antigen CD133 identifies such a tumorigenic population in a subset of glioblastoma patients. We conducted a prospective study to explore the prognostic potential of CSC analysis in glioblastoma patients.
  
  
  METHODS
  We investigated the relationship between the in vitro growth potential of glioblastoma CSCs and patient death or disease progression in tumors of 44 consecutive glioblastoma patients treated with complete or partial tumorectomy followed by radiotherapy combined with temozolomide treatment. Moreover, we evaluated by immunohistochemistry and immunofluorescence the prognostic value of the relative presence of CD133+ and CD133+/Ki67+ cells in patient tumors.
  
  
  RESULTS
  In vitro CSC generation and the presence of > or = 2% CD133+ cells in tumor lesions negatively correlated with overall (P = 0.0001 and 0.02, respectively) and progression-free (P = 0.0002 and 0.01, respectively) survival of patients. A very poor overall (P = 0.007) and progression-free (P = 0.001) survival was observed among patients whose tumors contained CD133+ cells expressing Ki67. Taking into account symptom duration, surgery type, age, O6-methylguanine-DNA methyltransferase promoter methylation, and p53 status, generation of CSCs and CD133/Ki67 coexpression emerged as highly significant independent prognostic factors, with an adjusted hazard ratio of 2.92 (95% confidence interval, 1.37-6.2; P = 0.005) and 4.48 (95% confidence interval, 1.68-11.9; P = 0.003), respectively.
  
  
  CONCLUSIONS
  The analysis of CSCs may predict the survival of glioblastoma patients. In vitro CSC generation and presence of CD133+/Ki67+ cells are two considerable prognostic factors of disease progression and poor clinical outcome.
authors.affiliation: Department of Neurosurgery, Catholic University of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pallini
authors.forename: Lucia
authors.initials: L
authors.lastname: Ricci-Vitiani
authors.forename: Giuseppe Luigi
authors.initials: GL
authors.lastname: Banna
authors.forename: Michele
authors.initials: M
authors.lastname: Signore
authors.forename: Dario
authors.initials: D
authors.lastname: Lombardi
authors.forename: Matilde
authors.initials: M
authors.lastname: Todaro
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stassi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Giulio
authors.initials: G
authors.lastname: Maira
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology*; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010455:Peptides / Q000032:analysis; D011446:Prospective Studies
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D019394:Ki-67 Antigen; C000606023:PROM1 protein, human; D010455:Peptides