title: Phosphorylated Akt expression is a prognostic marker in early-stage non-small cell lung cancer.
abstract: OBJECTIVE
  To determine the prognostic significance of pAkt expression in order to identify high-risk stage IB patients with non-small cell lung cancer (NSCLC) in an exploratory study.
  
  
  METHODS
  We identified 471 consecutive patients with stage IB primary NSCLC according to the American Joint Commission on Cancer 6th edition tumour-node-metastasis (TNM) staging system, who underwent surgical resection between 1990 and 2008. Patients who received neoadjuvant or adjuvant treatments were excluded. Pathology reports were reviewed, and pathological characteristics were extracted. Expression of phosphorylated Akt (pAkt) in both cytoplasmic and nuclear locations was assessed by immunohistochemistry, and clinicopathological factors were analysed against 10-year overall survival using Kaplan-Meier and Cox proportional hazards model.
  
  
  RESULTS
  455 (96.6%) cancers were adequate for pAkt immunohistochemical analysis. The prevalence of pAkt expression in the cytoplasm and nucleus of the cancers was 60.7% and 43.7%, respectively. Patients whose cancers expressed higher levels of cytoplasmic pAkt had a trend towards longer overall survival than those with lower levels (p=0.06). Conversely, patients whose cancers expressed higher levels of nuclear pAkt had a poorer prognosis than those with lower levels of expression (p=0.02). Combined low cytoplasmic/high nuclear expression of pAkt was an independent predictor of overall survival (HR=2.86 (95% CI 1.35 to 6.04); p=0.006) when modelled with age (HR=1.05 (95% CI 1.03 to 1.07); p<0.001), extent of operation (HR=2.11 (95% CI 1.48 to 3.01); p<0.001), visceral pleural invasion (HR=1.63 (95% CI 1.24 to 2.15); p<0.001), gender, tumour size, histopathological type and grade (p>0.05).
  
  
  CONCLUSIONS
  Level of expression of pAkt in the cytoplasm and nucleus is an independent prognostic factor that may help to select patients with high-risk disease.
authors.affiliation: Department of Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, , Sydney, New South Wales, Australia.
authors.forename: P Y
authors.initials: PY
authors.lastname: Yip
authors.forename: W A
authors.initials: WA
authors.lastname: Cooper
authors.forename: M R J
authors.initials: MR
authors.lastname: Kohonen-Corish
authors.forename: B P C
authors.initials: BP
authors.lastname: Lin
authors.forename: B C
authors.initials: BC
authors.lastname: McCaughan
authors.forename: M J
authors.initials: MJ
authors.lastname: Boyer
authors.forename: J G
authors.initials: JG
authors.lastname: Kench
authors.forename: L G
authors.initials: LG
authors.lastname: Horvath
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009517:New South Wales / Q000453:epidemiology; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D051057:Proto-Oncogene Proteins c-akt
keywords: Immunohistochemistry; Lung Cancer; Oncology