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Original article
The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer
  1. Muhammad Alamgeer1,2,
  2. Vinod Ganju1,2,
  3. Anette Szczepny2,
  4. Prudence A Russell3,
  5. Zdenka Prodanovic4,
  6. Beena Kumar4,
  7. Zoe Wainer5,
  8. Tracey Brown6,
  9. Michal Schneider-Kolsky7,
  10. Matthew Conron8,
  11. Gavin Wright5,
  12. D Neil Watkins2
  1. 1Department of Medical Oncology, Monash Medical Centre, East Bentleigh, Melbourne, Australia
  2. 2Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia
  3. 3Department of Pathology, St Vincent's Hospital, Fitzroy, Melbourne, Australia
  4. 4Department of Pathology, Monash Medical Centre, Clayton, Melbourne, Australia
  5. 5Department of Surgery, University of Melbourne, St Vincent's Hospital, Fitzroy, Melbourne, Australia
  6. 6Department of Biochemistry and Molecular Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Melbourne, Australia
  7. 7Department of Medical Imaging and Radiation Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Melbourne, Australia
  8. 8Department of Respiratory Medicine, St Vincent Hospital, Fitzroy, Melbourne, Australia
  1. Correspondence to Professor D Neil Watkins, Monash Institute of Medical Research, Monash University, 27-31 Wright St, Clayton, VIC 3168, Australia; neil.watkins{at}monash.edu and Dr Gavin Wright, Department of Surgical Oncology, St Vincent's Hospital, 55 Victoria Parade, Fitzroy, VIC 3065, Australia; gavin.wright{at}svhm.org.au

Abstract

Background Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC).

Methods A retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined.

Results We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7% and 50.7% of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively).

Conclusions Expression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.

  • Lung Cancer
  • Thoracic Surgery

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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