Twenty-eight percent of metastatic lymph nodes from occult primary tumors were HPV positive. There was no survival difference associated with HPV status. Most of the HPV-positive patients in this study were tobacco users who had similar survival to HPV-negative patients, so caution should be used in interpreting HPV status in these patients.
Objectives-No reliable molecular biomarker is currently available for clinical application in the management of head and neck cancer patients. The AKT/MTOR pathway is activated in 90-100% of HNSCC and could be promising biomarkers closely linked to cancer incidence.Methods-Oral mucosa from non-cancer patients were compared to HNSCC tumors and junctional zone mucosa. The candidate biomarkers MTOR, AKT, 4EBP1, and S6 kinase, signaling components upstream and downstream of MTOR that appear dysregulated in HNSCC were evaluated using immunohistochemistry (IHC) and western blot.Results-Expression of phosphorylated AKT and phosphorylated MTOR were significantly higher in cancer patient tumors compared to non-cancer oral mucosa samples (p=0.004 and p=0.026 respectively) by western. pMTOR and p4EBP1 expression were higher in patient junctional zones compared to tumors (p=0.017 and p=0.022 respectively) and no difference in p-AKT or p-S6 expression in HNSCC patients' junctional zone compared to tumors. IHC demonstrated p-MTOR expression was 81.9% sensitive and 100% specific in differentiating cancer from non-cancer mucosa, while p-4EBP1 expression by IHC was only 50.0% sensitive and 95.5% specific in differentiating normal mucosa from HNSCC (p<0.01).Conclusions-Phosphorylated MTOR appears to be a reliable biomarker by both western (p=0.026) and IHC in human head and neck cancer (p<0.001). Moreover, phosphorylated AKT, which is immediately upstream of MTOR, is a potential biomarker that should be further studied. Clinical trials with MTOR inhibitors are being evaluated for HNSCC, and selecting patients that are likely to respond to these inhibitors requires identifying and validating predictive biomarkers of response.
Curcumin appears to inhibit skin SCCa growth and blocks tumor progression by inhibiting pS6 even when gavage is used to deliver curcumin, indicating even more significant effects in future experiments with local application.
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