Phosphorylated 4E-binding protein 1 (p-4E-BP1): a novel prognostic marker in human astrocytomas - Archive ouverte HAL
Article Dans Une Revue Histopathology Année : 2012

Phosphorylated 4E-binding protein 1 (p-4E-BP1): a novel prognostic marker in human astrocytomas

Penelope Korkolopoulou
  • Fonction : Auteur
Georgia Levidou
  • Fonction : Auteur
Christina Piperi
  • Fonction : Auteur
Christos Adamopoulos
  • Fonction : Auteur
Vassilis Samaras
  • Fonction : Auteur
Efstathios Boviatsis
  • Fonction : Auteur
Irene Thymara
  • Fonction : Auteur
Eleni-Andriana Trigka
  • Fonction : Auteur
Stratigoula Sakellariou
  • Fonction : Auteur
Nikolaos Kavantzas
  • Fonction : Auteur
Efstratios Patsouris
  • Fonction : Auteur
Angelica A. Saetta
  • Fonction : Auteur

Résumé

Korkolopoulou P, Levidou G, El-Habr E A, Piperi C, Adamopoulos C, Samaras V, Boviatsis E, Thymara I, Trigka E-A, Sakellariou S, Kavantzas N, Patsouris E & Saetta A A ?(2012) Histopathology similar to 61, 293305 Phosphorylated 4E-binding protein 1 (p-4E-BP1): a novel prognostic marker in human astrocytomas Aims: To investigate the significance of the mammalian target of rapamycin (mTOR) pathway in astrocytic tumours, published information in this context being limited, especially regarding phosphorylated 4E-binding protein (p-4E-BP) 1. Methods and results: Paraffin-embedded tissue from 111 patients with astroglial tumours (grades IIIV) was investigated for the association of phosphorylated mTOR (p-mTOR) signalling components with phosphorylated extracellular signal-related kinase 1/2 (p-ERK1/2) and phosphorylated AKT (p-AKT) expression, clinicopathological features, angiogenesis, isocitrate dehydrogenase 1 (IDH1)-R132H, and survival. Expression was also quantified by western blot analysis in 12 cases and in three primary glioma cell cultures following rapamycin treatment. p-mTOR expression correlated with p-4E-BP1 expression and marginally with p-p70S6K expression. p-4E-BP1 expression increased with tumour grade. Rapamycin induced a decline in phosphorylation levels of all three proteins. Nuclear p-AKT and cytoplasmic p-ERK1/2 immunoexpression correlated with p-4E-BP1 expression, whereas cytoplasmic p-AKT expression correlated with p-p70S6K expression. All three proteins were associated with increased angiogenesis but not with IDH1-R132H expression status. p-mTOR adversely affected overall and disease-free survival in univariate analysis. In multivariate survival analysis, the presence of p-4E-BP1 predicted shortened overall survival in the entire cohort and glioblastomas. Conclusions: mTOR signalling components are differentially involved in the acquisition of a more aggressive and angiogenic phenotype in astrocytic tumours. Moreover, p-4E-BP1 emerges as a novel prognostic marker, which might aid in the selection of patients who are more likely to benefit from therapy with mTOR inhibitors.

Dates et versions

hal-01541443 , version 1 (19-06-2017)

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Citer

Penelope Korkolopoulou, Georgia Levidou, Elias A. El-Habr, Christina Piperi, Christos Adamopoulos, et al.. Phosphorylated 4E-binding protein 1 (p-4E-BP1): a novel prognostic marker in human astrocytomas. Histopathology, 2012, 61 (2), pp.293-305. ⟨10.1111/j.1365-2559.2012.04236.x⟩. ⟨hal-01541443⟩
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