Relationship between the Endogenous Hypoxic Markers Hypoxia Inducible Factor-1alpha, Carbonic Anhydrase IX, and Epithelial Mesenchymal Transition Regulator TWIST Expression in Non-small Cell Lung Cancer

ABSTRACT

BACKGROUND: The epithelial mesenchymal transition (EMT) is intimately associated with tumor hypoxia. The present study was conducted to investigate the immunohistochemical relationship between hypoxic and EMT-related molecules in non-small cell lung carcinoma (NSCLC). METHODS: Immunohistochemical staining for hypoxia inducible factor (HIF)-1alpha, carbonic anhydrase (CA) IX, TWIST, and E-cadherin proteins was performed in 146 cases of NSCLC (80 cases of adenocarcinoma and 66 cases of squamous cell carcinoma) using tissue microarray blocks. RESULTS: HIF-1alpha, TWIST, CA IX, and E-cadherin were expressed in 58 (40%), 90 (62%), 82 (56%), and 36 (25%) of 146 NSCLC cases, respectively. TWIST expression was positively correlated with HIF-1alpha expression (p = 0.03) and inversely correlated with E-cadherin expression (p < 0.01). TWIST and CA IX expression were not significantly interrelated, but each showed a relationship with histological tumor grade. However, the expression of these molecules had no significant effect on clinical staging or patient survival. CONCLUSIONS: Although TWIST expression was correlated positively with HIF-1alpha expression and inversely correlated with E-cadherin, HIF-1alpha expression was not associated with E-cadherin expression. However, considering the relationship between HIF-1alpha and TWIST expression, further studies should be performed to demonstrate the role of hypoxia-induced EMT in NSCLC.