PI3‐kinase pathway biomarkers in oral cancer and tumor immune cells

BACKGROUND: This study investigated the hypothesis that phosphoinositide 3-kinase (PI3-kinase) pathway dysregulation in either head and neck cancer cells and/or tumor infiltrating immune cells would influence outcomes of patients with surgically treated oral tongue squamous cell carcinomas (SCC). METHODS: We constructed tissue microarrays containing 123 oral tongue SCC samples and performed immunohistochemistry using antibodies against 7 PI3-kinase pathway markers: phosphatase and tensin homolog (PTEN), Akt, p-Akt, mammalian target of rapamycin (mTOR), phosphorylated-mammalian target of rapamycin (p-mTOR), survivin, and Ki-67). Expression levels in cancer cells or tumor infiltrating immune cells were correlated with outcomes. RESULTS: Higher levels of PTEN expression in immune cells were significantly associated with improved recurrence-free survival (heart rate (HR) = 0.45, 95% confidence interval (CI) 0.23-0.90, P = .03), and overall survival (HR = 0.34, 95% CI 0.15-0.76, P = .01) on univariate and multicovariate models. CONCLUSIONS: We identified a novel, negative prognostic role of PI3-kinase activation (as determined by PTEN loss) in oral SCC infiltrating immune cells. These findings could be relevant for clinical development of PI-3 kinase inhibitors for this disease.