title: High expression of mammalian target of rapamycin is associated with better outcome for patients with early stage lung adenocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pathology, Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520-8023, USA.
authors.forename: Valsamo K
authors.initials: VK
authors.lastname: Anagnostou
authors.forename: Gerold
authors.initials: G
authors.lastname: Bepler
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Syrigos
authors.forename: Lynn
authors.initials: L
authors.lastname: Tanoue
authors.forename: Scott
authors.initials: S
authors.lastname: Gettinger
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Homer
authors.forename: Daniel
authors.initials: D
authors.lastname: Boffa
authors.forename: Frank
authors.initials: F
authors.lastname: Detterbeck
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D011494:Protein Kinases / Q000096:biosynthesis*; D058570:TOR Serine-Threonine Kinases; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases