A comprehensive immunohistochemical approach of AKT/mTOR pathway and p-STAT3 in mycosis fungoides - 17/08/13
Abstract |
Background |
Although the expression pattern of phosphorylated (p)-mTOR pathway components has attracted scientific interest in several neoplasms, to our knowledge, there is no published information regarding its significance in mycosis fungoides (MF).
Objective |
We sought to perform a comprehensive simultaneous assessment of key members of AKT/mTOR pathway along with p-extracellular signal-regulated kinase (ERK), NOTCH1, and p-STAT3 in patients with MF.
Methods |
In all, 54 skin biopsy specimens (21 tumors, 30 plaques, and 3 folliculotropic MF) from 50 patients with MF were analyzed immunohistochemically for p-mTOR, its upstream p-AKT, its downstream effectors p-p70S6K and p-4E-BP1, and for p-ERK1/2, NOTCH1, and p-STAT3.
Results |
p-mTOR was coexpressed with p-p70S6K in 67.3% of lesions, but coexpression with other molecules was less common. p-p70S6K and marginally NOTCH1 displayed higher H-scores in tumors than in plaques. Significant correlations were recorded between p-ERK and p-4E-BP1, as well as between NOTCH1 and p-p70S6K or p-4E-BP1. NOTCH1, p-4E-BP1, and p-p70S6K expression were associated with advanced stage. In survival analysis simultaneous overexpression of p-AKT and p-p70S6K, along with p-4E-BP1 positivity, adversely affected cancer-specific, disease-free, and progression-free survival in advanced-stage cases.
Limitations |
A limitation may be the small number of cases included in our investigation, precluding multivariate survival analysis.
Conclusions |
Activation of AKT/mTOR pathway in MF appears to be correlated with NOTCH1, p-ERK, and p-STAT3 and is implicated in the acquisition of a more aggressive phenotype. The combination of p-AKT, p-p70S6K, and p-4E-BP1 emerges as a significant potential prognostic marker in patients with advanced stage.
Le texte complet de cet article est disponible en PDF.Key words : AKT, extracellular signal-regulated kinase, mTOR, mycosis fungoides, NOTCH1, p70S6K, STAT3, 4E-BP1
Abbreviations used : CSS, DFS, ERK, MF, p, PFS
Plan
Funding sources: None. |
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Conflicts of interest: None declared. |
Vol 69 - N° 3
P. 375-384 - septembre 2013 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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