A comprehensive immunohistochemical approach of AKT/mTOR pathway and p-STAT3 in mycosis fungoides

作者：Levidou Georgia^*; Siakantaris Marina; Papadaki Theodora; Papadavid Evangelia; Vassilakopoulos Theodoros P; Angelopoulou Maria K; Marinos Leonidas; Nikolaou Vassiliki; Economidi Aphroditi; Antoniou Christina; Patsouris Efstratios; Korkolopoulou Penelope

来源：Journal of the American Academy of Dermatology, 2013, 69(3): 375-384.

DOI：10.1016/j.jaad.2013.04.027

• AKT
• extracellular signal-regulated kinase
• mTOR
• mycosis fungoides
• NOTCH1
• p70S6K
• STAT3
• 4E-BP1

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). %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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-4EBP1 positivity, adversely affected cancer-specific, disease-free, and progression-free survival in advanced-stage cases. %26lt;br%26gt;Limitations: A limitation may be the small number of cases included in our investigation, precluding multivariate survival analysis. %26lt;br%26gt;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.

• 出版日期2013-9