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Phosphorylated Akt expression is a prognostic marker in early-stage non-small cell lung cancer
  1. P Y Yip1,2,3,
  2. W A Cooper4,5,
  3. M R J Kohonen-Corish2,5,6,
  4. B P C Lin7,
  5. B C McCaughan3,8,
  6. M J Boyer1,3,
  7. J G Kench2,3,4,
  8. L G Horvath1,2,3
  1. 1Department of Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
  2. 2The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Sydney, New South Wales, Australia
  3. 3Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
  4. 4Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
  5. 5School of Medicine, University of Western Sydney, Sydney, New South Wales, Australia
  6. 6St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
  7. 7Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
  8. 8Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
  1. Correspondence to Associate Professor Lisa Horvath, Sydney Cancer Centre, Level 6, Gloucester House, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW 2050, Australia; lisa.horvath{at}sswahs.nsw.gov.au

Abstract

Aims 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.

  • Lung Cancer
  • Immunohistochemistry
  • Oncology

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