title: A comprehensive immunohistochemical approach of AKT/mTOR pathway and p-STAT3 in mycosis fungoides.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, University of Athens, Medical School, Athens, Greece. glevidou@yahoo.gr
authors.forename: Georgia
authors.initials: G
authors.lastname: Levidou
authors.forename: Marina
authors.initials: M
authors.lastname: Siakantaris
authors.forename: Theodora
authors.initials: T
authors.lastname: Papadaki
authors.forename: Evangelia
authors.initials: E
authors.lastname: Papadavid
authors.forename: Theodoros P
authors.initials: TP
authors.lastname: Vassilakopoulos
authors.forename: Maria K
authors.initials: MK
authors.lastname: Angelopoulou
authors.forename: Leonidas
authors.initials: L
authors.lastname: Marinos
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Nikolaou
authors.forename: Aphroditi
authors.initials: A
authors.lastname: Economidi
authors.forename: Christina
authors.initials: C
authors.lastname: Antoniou
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009182:Mycosis Fungoides / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C497761:NOTCH1 protein, human; D010750:Phosphoproteins; D051881:Receptor, Notch1; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: 4E-BP1; AKT; CSS; DFS; ERK; MF; NOTCH1; PFS; STAT3; cancer-specific survival; disease-free survival; extracellular signal-regulated kinase; mTOR; mycosis fungoides; p; p70S6K; phosphorylated; progression-free survival