Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme.
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.
Pallini
Roberto
R
Department of Neurosurgery, Catholic University of Rome, Rome, Italy.
Ricci-Vitiani
Lucia
L
Banna
Giuseppe Luigi
GL
Signore
Michele
M
Lombardi
Dario
D
Todaro
Matilde
M
Stassi
Giorgio
G
Martini
Maurizio
M
Maira
Giulio
G
Larocca
Luigi Maria
LM
De Maria
Ruggero
R
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
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D019394:Ki-67 Antigen; C000606023:PROM1 protein, human; D010455:Peptides