title: Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: a verification study.
abstract: BACKGROUND
  A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival.
  
  
  METHODS
  Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells×staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated.
  
  
  RESULTS
  101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p=0.024) and mTOR staining (p=0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p=0.037 and p=0.020, respectively).
  
  
  CONCLUSIONS
  Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway.
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland. kgately@stjames.ie
authors.forename: K
authors.initials: K
authors.lastname: Gately
authors.forename: B
authors.initials: B
authors.lastname: Al-Alao
authors.lastname: T Dhillon
authors.forename: F
authors.initials: F
authors.lastname: Mauri
authors.forename: S
authors.initials: S
authors.lastname: Cuffe
authors.forename: M
authors.initials: M
authors.lastname: Seckl
authors.forename: K
authors.initials: K
authors.lastname: O'Byrne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001808:Blood Vessels / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D058570:TOR Serine-Threonine Kinases / Q000032:analysis* / Q000502:physiology
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases