A comprehensive immunohistochemical approach of AKT/mTOR pathway and p-STAT3 in mycosis fungoides - 17/08/13
, Marina Siakantaris, PhD b, Theodora Papadaki, PhD c, Evangelia Papadavid, PhD d, Theodoros P. Vassilakopoulos, PhD e, Maria K. Angelopoulou, PhD e, Leonidas Marinos, MD c, Vassiliki Nikolaou, MD f, Aphroditi Economidi, MD f, Christina Antoniou, PhD f, Efstratios Patsouris, PhD a, Penelope Korkolopoulou, PhD aAbstract |
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 numéro
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