High Expression of Mammalian Target of Rapamycin Is Associated with Better Outcome for Patients with Early Stage Lung Adenocarcinoma

Purpose: Mammalian target of rapamycin (mTOR) is a key kinase downstream of phosphoinositide 3-kinase (PI3K)/AKT predominantly involved in translational control in the presence of nutrients and energy. Despite the well known role of mTOR in carcinogenesis, its prognostic potential in lung cancer has not been investigated. Here, we quantitatively assessed mTOR protein expression in two large data sets to investigate the impact of mTOR expression on patient survival. Experimental Design: Automated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expression, was used to assess mTOR expression in a training cohort of 167 lung cancer patients, An independent cohort of 235 lung cancer patients (from a second institution) was used for validation. Results: Tumors expressed mTOR in the cytoplasm in 56% and 50% of the cases in training and validation cohorts, respectively; mTOR expression was not associated with standard clinical or pathologic characteristics. Patients with high mTOR expression had a longer median overall survival compared with the low expressers (52.7 versus 38.5 months; log rank P = 0.06), which was more prominent in the adenocarcinoma group (55.7 versus 38.88 months; log rank P = 0.018). Multivariate analysis revealed an independent lower risk of death for adenocarcinoma and adenocarcinoma stage IA patients with mTOR-expressing tumors (hazard ratio, 0.48; 95% confidence interval, 0.24-0.98; P = 0.04, and hazard ratio, 0.12; 95% confidence interval, 0.03-0.72; P = 0.019, respectively). Conclusions: mTOR expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of lung adenocarcinoma patients as well as incorporation of mTOR into clinical decisions.