Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma patients of the temozolomide era.
PLoS One
; 7(3): e33684, 2012.
Article
en En
| MEDLINE
| ID: mdl-22479427
ABSTRACT
INTRODUCTION:
Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed.METHODS:
Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age, extent of resection, Karnofsky performance scale (KPS), and treatment on overall survival.RESULTS:
Sixty-five percent of patients were men with median age of 63 years, and 70% had KPS≥80. Most patients (81%) received standard treatment (temozolomide with concurrent radiation). A total of 72 (47%) patients had retained PTEN expression. Median overall survival (OS) was 19.1 months (95% CI 15.0-22.5). Median survival of 20.0 months (95% CI 15.0-25.5) and 18.2 months (95% CI 13.0-25.7) was observed in PTEN retained and PTEN loss patients, respectively (pâ=â.71). PTEN loss patients were also found to have amplifications of EGFR gene more frequently than patients with retained PTEN (70.8% vs. 47.8%, pâ=â.01). Multivariate analysis showed that older age (HR 1.64, CI 1.02-2.63, pâ=â.04), low KPS (HR 3.57, CI 2.20-5.79, p<.0001), and lack of standard treatment (HR 3.98, CI 2.38-6.65, p<.0001) yielded worse survival. PTEN loss was not prognostic of overall survival (HR 1.31, CI 0.85-2.03, pâ=â.22).CONCLUSIONS:
Loss of expression of PTEN does not confer poor overall survival in the temozolomide era. These findings imply a complex and non-linear molecular relationship between PTEN, its regulators and effectors in the tumorigenesis of glioblastoma. Additionally, there is evidence that temozolomide may be more effective in eradicating GBM cancer cells with PTEN loss and hence, level the outcomes between the PTEN retained and loss groups.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_brain_nervous_system_cancer
Asunto principal:
Glioblastoma
/
Fosfohidrolasa PTEN
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos