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Phosphorylated 4E‐binding protein 1 (p‐4E‐BP1): a novel prognostic marker in human astrocytomas
Author(s) -
Korkolopoulou Penelope,
Levidou Georgia,
ElHabr Elias A,
Piperi Christina,
Adamopoulos Christos,
Samaras Vassilis,
Boviatsis Efstathios,
Thymara Irene,
Trigka EleniAndriana,
Sakellariou Stratigoula,
Kavantzas Nikolaos,
Patsouris Efstratios,
Saetta Angelica A
Publication year - 2012
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2012.04236.x
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , phosphorylation , angiogenesis , cancer research , biology , mtorc2 , western blot , kinase , glioma , pathology , signal transduction , medicine , mtorc1 , microbiology and biotechnology , biochemistry , gene
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 61, 293–305 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 II–IV) 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.