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  • Title: The PI3K/AKT/mTOR signalling pathway is active in salivary gland cancer and implies different functions and prognoses depending on cell localisation.
    Author: Ettl T, Schwarz-Furlan S, Haubner F, Müller S, Zenk J, Gosau M, Reichert TE, Zeitler K.
    Journal: Oral Oncol; 2012 Sep; 48(9):822-30. PubMed ID: 22445095.
    Abstract:
    OBJECTIVES: 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. MATERIALS AND 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. RESULTS AND CONCLUSION: 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.
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