Diverging prognostic impacts of hypoxic markers according to NSCLC histology.

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.