Clinical Outcome in Pediatric Glial and Embryonal Brain Tumors Correlates With In Vitro Multi-Passageable Neurosphere Formation

作者:Panosyan Eduard H; Laks Dan R; Masterman Smith Michael; Mottahedeh Jack; Yong William H; Cloughesy Timothy F; Lazareff Jorge A; Mischel Paul S; Moore Theodore B; Kornblum Harley I*
来源:Pediatric Blood and Cancer, 2010, 55(4): 644-651.
DOI:10.1002/pbc.22627

摘要

Background. Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric brain tumors is unknown Methods. Established neurosphere conditions were used for culturing samples from glial, embryonal and mixed glioneuronal tumors from 56 pediatric patients Potential associations between neurosphere formation and clinical outcome were analyzed retrospectively Results. Thirty-seven percent of all samples formed renewable neurospheres Analysis of available clinical outcome data from 51 patients demonstrated significantly increased hazard ratios (HR) for both disease progression (HR = 9 9, P < 0 001) and death (HR = 16 6, P < 0 01) in the neurosphere forming group Furthermore, neurosphere formation correlated with adverse progression free survival (PFS) in glial and embryonal tumors, but not in mixed glioneuronal tumors Overall survival (OS) was significantly worse for neurosphere-forming patients with embryonal tumors, as a group and amongst the subgroup with medulloblastoma, but not in die glial group Multivariate analysis showed that neurosphere formation was associated with diminished PFS and OS independent of age, gender, or treatment Neurosphere formation was an independent predictor of diminished PFS of ghat tumors after adjusting for grade Multivariate analysis, adjusting for both Ki67 staining and neurosphere formation, demonstrated that neuro-sphere formation remained predictive of progression whereas Ki67 did not Conclusions. Neurosphere formation is more predictive of pediatric brain tumor progression t

  • 出版日期2010-10