title: The PI3K/AKT/mTOR signalling pathway is active in salivary gland cancer and implies different functions and prognoses depending on cell localisation.
abstract: OBJECTIVE
  The PI3K/AKT/mTOR signalling axis controls cell proliferation and survival and has achieved major importance as a target for cancer therapy. This investigation evaluated the expression of the major components P-AKT, P-mTOR, PI3K and P-S6rp in salivary gland cancer.
  
  
  METHODS
  Immunohistochemical expression of P-AKT, P-mTOR, PI3K and P-S6rp was evaluated and correlated to clinicopathological parameters and survival of 272 patients with salivary gland carcinomas.
  
  
  CONCLUSIONS
  Analysis of all tumours together revealed an increased expression of all components of the pathway in comparison to normal salivary gland control tissue. Nuclear expression of P-AKT was associated with young age, localised tumour stage, absence of lymph node metastases and favourable prognosis. On the contrary, cytoplasmic P-AKT displayed unfavourable tumour characteristics like high-grade malignancy, and worse overall survival. In comparison to cytoplasmic/membrane mTOR expression, nuclear P-mTOR was associated with absence of lymph node metastases and higher survival rates. PI3K and P-S6rp were exclusively found in the cytoplasm. Expression of P-S6rp was correlated to increased age, advanced tumour size and lymph node metastases. In all tumours together, nuclear P-AKT positively correlated with nuclear P-mTOR, whereas P-S6rp was associated with expression of PI3K and cytoplasmic P-AKT. In acinic cell carcinoma, cytoplasmic expression of P-AKT, P-mTOR, PI3K and P-S6rp was positively associated with each other. In conclusion, PI3K/AKT/mTOR signalling is active in salivary gland cancer and might function as a target for personalised therapy. P-AKT and P-mTOR possess distinct molecular functions with impact on prognosis depending on their cellular localisation.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. tobias.ettl@klinik.uni-regensburg.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Ettl
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwarz-Furlan
authors.forename: Frank
authors.initials: F
authors.lastname: Haubner
authors.forename: Steffen
authors.initials: S
authors.lastname: Müller
authors.forename: Johannes
authors.initials: J
authors.lastname: Zenk
authors.forename: Martin
authors.initials: M
authors.lastname: Gosau
authors.forename: Torsten E
authors.initials: TE
authors.lastname: Reichert
authors.forename: Katharina
authors.initials: K
authors.lastname: Zeitler
mesh_terms: D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human