title: Immunohistochemical evaluation of the mTOR pathway in intra-oral minor salivary gland neoplasms.
abstract: OBJECTIVE
  The aim of this study was to investigate the expression of upstream and downstream molecules of the oncogenic mTOR signaling pathway in intra-oral minor salivary gland tumors (SGTs).
  
  
  METHODS
  Tissue samples consisted of 39 malignant and 13 benign minor SGTs, and 8 controls of normal minor salivary glands (NMSG). An immunohistochemical analysis for phosphorylated Akt, 4EBP1 and S6 (total and phosphorylated), and eIF4E was performed.
  
  
  RESULTS
  Expression of pAkt and 4EBP1 was observed in all SGTs and in most NMSG. p4EBP1 was detected in almost all SGT cases, NMSG being negative. S6 immunoreactivity was observed in 37.5% of NMSG, 92.3% of benign and 100% of malignant SGTs, while pS6 expression was observed in 77% of benign and 95% of malignant SGTs, but not in NMSG. Finally, eIF4E was expressed in 12.5% of NMSG, 69.2% of benign, and 76.9% of malignant tumors. All molecules studied had statistically significantly lower expression in NMSG compared with SGTs. Moreover, malignant neoplasms received higher scores compared with benign tumors for all molecules with the exception of eIF4E.
  
  
  CONCLUSIONS
  The mTOR signaling pathway is activated in SGTs, especially in malignancies. Therefore, the possible therapeutic role of targeting the mTOR pathway by rapamycin analogs in SGTs needs further investigation.
authors.affiliation: Department of Oral Medicine and Pathology, Dental School, University of Athens, Athens, Greece. info@oralmedicine.gr, sdiamanti@gmail.com.|Oral Medicine Department, 251 General Air Force and VA Hospital, Athens, Greece. info@oralmedicine.gr, sdiamanti@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Diamanti
authors.affiliation: Department of Oral Medicine and Pathology, Dental School, University of Athens, Athens, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Nikitakis
authors.affiliation: Department of Pathology, Medical School, University of Athens, Athens, Greece.|Department of Pathology and Cytology, Carolinska University Hospital and Karolinska Institute, Solna, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Rassidakis
authors.affiliation: Oral Medicine Department, 251 General Air Force and VA Hospital, Athens, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Doulis
authors.affiliation: Department of Oral Medicine and Pathology, Dental School, University of Athens, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Sklavounou
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D012468:Salivary Gland Neoplasms / Q000378:metabolism*; D012470:Salivary Glands, Minor; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000032:analysis*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: 4E-binding protein 1; Akt; S6; eIF4E; immunohistochemistry; intra-oral minor salivary gland neoplasms; mTOR