Prognostic implications of the phosphatidylinositol 3-kinase/Akt signaling pathway in oral squamous cell carcinoma: overexpression of p-mTOR indicates an adverse prognosis

ABSTRACT

Background: The development of oral cavity cancer is related to the accumulation of genetic alterations. The activation of AKT is associated with the proliferation and progression of many malignancies. It is thought that MAP kinases, together with the PI3K/AKT/mTOR signaling pathway, promote uncoordinated proliferation via inhibition of PTEN, thus increasing cell survival and mediating cancer progression. However, there are few studies regarding the expression of these proteins in oral squamous cell carcinoma (SCC). Methods: The expression of PI3K, p-mTOR, p-AKT, p-MAPK, and PTEN in 125 oral SCCs, including gingival, palate hard, and alveolar ridge tumors, was examined by immunohistochemistry and correlated with clinicopathological data and survival rates. Results: We observed PI3K, p-mTOR, p-MAPK, p-AKT, and PTEN positive staining in the cytoplasm of most SCC (92.4%, 88.2%, 88.3%, 94.2%, and 25%, respectively). Positive nuclear staining was observed for p-mTOR, PTEN, p-AKT, and p-MAPK (42.9%, 72%, 64.2%, and 58.2%, respectively). Only p-mTOR protein expression was observed on the cell membrane and was present in 44.5% of cases. A statistically significant correlation was found between p-MAPK expression and SCC clinicopathological stages III and IV (p = 0.0042). Lower rates of disease-free survival were found in patients with SCC III / IV (p = 0.001). Patients with positive nuclear staining of p-mTOR displayed a significant increase in disease-free survival rates. Discussion: The identification of prognostic and predictive markers is clinically important because oral cancer is a group of heterogeneous diseases with various biological and clinical characteristics. Conclusion: Our findings suggest that the PI3K/AKT pathway is activated in gingival, hard palate, and alveolar ridge SCCs. We have demonstrated that p-mTOR expression can function as a biomarker for survival in oral SCCs and could be a promising therapeutic target in oral SCC treatment (AU)