- 作者：Georgia Levidou ; Marina Siakantaris ; Theodora Papadaki ; Evangelia Papadavid ; Theodoros P. Vassilakopoulos ; Maria K. Angelopoulou ; Leonidas Marinos ; Vassiliki Nikolaou ; Aphroditi Economidi ; Christina Antoniou ; Efstratios Patsouris ; Penelope Korkolopoulou
- 关键词：AKT ; extracellular signal-regulated kinase ; mTOR ; mycosis fungoides ; NOTCH1 ; p70S6K ; STAT3 ; 4E-BP1
- 刊名：Journal of the American Academy of Dermatology
- 出版年：2013
- 出版时间：September, 2013
- 年：2013
- 卷：69
- 期：3
- 页码：375-384
- 全文大小：1263 K
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.