title: The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer.
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.
authors.affiliation: Department of Medical Oncology, Monash Medical Centre, , East Bentleigh, Melbourne, Australia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Alamgeer
authors.forename: Vinod
authors.initials: V
authors.lastname: Ganju
authors.forename: Anette
authors.initials: A
authors.lastname: Szczepny
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Russell
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Prodanovic
authors.forename: Beena
authors.initials: B
authors.lastname: Kumar
authors.forename: Zoe
authors.initials: Z
authors.lastname: Wainer
authors.forename: Tracey
authors.initials: T
authors.lastname: Brown
authors.forename: Michal
authors.initials: M
authors.lastname: Schneider-Kolsky
authors.forename: Matthew
authors.initials: M
authors.lastname: Conron
authors.forename: Gavin
authors.initials: G
authors.lastname: Wright
authors.forename: D Neil
authors.initials: DN
authors.lastname: Watkins
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000032:analysis*; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000032:analysis*; D016016:Proportional Hazards Models; D012008:Recurrence; D050697:Retinal Dehydrogenase; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: Lung Cancer; Thoracic Surgery