| dc.description.abstract | Head and neck cancers are malignancies that arise in pharynx, larynx, paranasal sinuses, nasal cavity and oral cavity. Oral cancers account for 40% of head and neck cancers and consist of malignancies arising from buccal mucosa, gingiva, floor of the mouth, tongue, palate, and lip. The most common histological variant of oral cancer is oral squamous cell carcinoma (OSCC). The global incidence rate of OSCC is high particularly in the developing countries. It is growing at an alarming rate, indicating the need for more efficient methods for prevention, early detection and management. Despite the easier access and clear visibility of the oral cavity, OSCCs are usually diagnosed at advanced stage. In addition, the metastatic spread would also affect the 5-year survival and most of the times recurrence and metastasis is seen in the first two years after initial diagnosis. Patients who survive more than 5 years have high risk for recurrence, loco-regional metastasis to lymph nodes and often have a compromised quality of life. Though there is advancement in diagnostic and treatment strategies, no reliable and established methods are currently available to stratify the OSCC patients and to predict prognosis. From few decades, tumor-node-metastasis (TNM) staging and histopathological grading systems were the standard tools used to predict prognosis and to guide the selection of appropriate treatment methods. More recently, depth of invasion (DOI) and extranodal extension (ENE) parameters were included in the latest edition of TNM staging. Despite their inclusion, they still do not provide a robust stratification of OSCC patients. There were also proposal to use a few other grading systems (various pathological parameters), such as tumor budding, pattern of invasion and perineural invasion as a prognostic parameters for OSCC, but they were shown to be indecisive and disputable. Ribosomal protein S6 is a key downstream molecule of mechanistic/mammalian target of rapamycin (mTOR) pathway in OSCCs. Despite the fact that phosphorylation of S6 (pS6) is one of the end-point indicators of the activation of mTOR pathway, the major oncogenic (mitogenic) pathway in OSCC, there is a paucity of studies done on its prognostic significance in OSCC. Therefore, using immunohistochemistry (IHC), the current study aimed to examine the expression profile and prognostic significance of pS6 (at 235 and 236 serine sites) protein in OSCC. Cytoplasmic expression of pS6 at Ser235/236 was detected in 80.2% of the OSCC cases at tumor center (TC) and in 66.3% of samples at the tumor invading front (TIF) region. The higher expression of expression of pS6 at TIF correlated with the worst pattern of invasion (p=0.012). Additionally, higher expression of pS6 at TIF was marginally associated with reduced overall- and recurrence free-survival probabilities for OSCC patients. In conclusion, our study corroborates previous findings indicating that activation of the mTOR signaling is a common event in OSCC. Correlation between high pS6 expression at TIF with the worst pattern of invasion and reduced probabilities for overall and recurrence free survival indicate that activation of mTORC1 arm of mTOR pathway might contribute to an aggressive tumor phenotype. In future, validation of these findings using a large cohort of patients might be useful in prognostication and guiding therapy for OSCC patients. | eng |