title: Diverging prognostic impacts of hypoxic markers according to NSCLC histology.
abstract: 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).
  
  
  CONCLUSIONS
  These markers show highly diverging prognostic impacts between histological subgroups and between tumor and stromal compartments in NSCLC.
authors.affiliation: Institute of Clinical Medicine, University of Tromso, Norway. sigve.andersen@uit.no
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.forename: Marte
authors.initials: M
authors.lastname: Eilertsen
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Shibli
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C089226:CA9 protein, human