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).

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