Diverging prognostic impacts of hypoxic markers according to NSCLC histology

Lung Cancer. 2011 Jun;72(3):294-302. doi: 10.1016/j.lungcan.2010.10.006. Epub 2010 Nov 13.


Background: We aimed to explore the prognostic impact of the hypoxia induced factors (HIFαs) 1-2 and the metabolic HIF-regulated glucose transporter GLUT1, lactate dehydrogenase 5 (LDH5) and carbonic anhydrase IX (CAIX) in non-small cell lung cancer (NSCLC).

Methods: Tumor and stroma tissue samples from 335 unselected patients with stage I-IIIA NSCLC were obtained and tissue microarrays constructed. Immunohistochemistry was used to evaluate expression.

Results: For squamous cell carcinoma patients, high tumor cell expression of HIF1α and low stromal cell expression of HIF1α and HIF2α correlated significantly with a poor disease-specific survival (DSS) in both univariate (tumor HIF1α, P=0.001; stromal HIF1α, P=0.009; stromal HIF2α, P=0.005) and multivariate analyses (tumor HIF1α, HR=3.3, P=0.001; stromal HIF1α, HR=2.1, P=0.008; stromal HIF2α, HR 2.3, P=0.005). Among adenocarcinoma patients high tumor expression of GLUT1 and low stromal expression of LDH5 correlated significantly with a poor DSS in both univariate (GLUT1, P=0.01; LDH5, P=0.03) and multivariate analyses (GLUT1, HR=1.9, P=0.046; LDH5, HR=2.3, P=0.03).

Conclusion: These markers show highly diverging prognostic impacts between histological subgroups and between tumor and stromal compartments in NSCLC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers, Tumor / metabolism*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Female
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Lactate Dehydrogenase 5
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Male
  • Microarray Analysis
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis


  • Antigens, Neoplasm
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Isoenzymes
  • endothelial PAS domain-containing protein 1
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases