The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer

Thorax. 2013 Dec;68(12):1095-104. doi: 10.1136/thoraxjnl-2012-203021. Epub 2013 Jul 22.

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.

Keywords: Lung Cancer; Thoracic Surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Aged, 80 and over
  • Aldehyde Dehydrogenase / analysis*
  • Aldehyde Dehydrogenase 1 Family
  • Antigens, CD / analysis*
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Disease-Free Survival
  • Female
  • Glycoproteins / analysis*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Peptides / analysis*
  • Proportional Hazards Models
  • Recurrence
  • Retinal Dehydrogenase
  • Retrospective Studies
  • Risk Factors

Substances

  • AC133 Antigen
  • Antigens, CD
  • Biomarkers, Tumor
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Aldehyde Dehydrogenase 1 Family
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase