Korean J Pathol.  2010 Oct;44(5):469-476.

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

Affiliations
  • 1Department of Pathology, Pusan National University School of Medicine, Busan, Korea. hudsn@chollian.net, cnlee@pusan.ac.kr
  • 2Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea.
  • 3Medical Research Institute, Pusan National University, Busan, Korea.
  • 4Department of Thoracic Surgery, Pusan National University School of Medicine, Busan, Korea.

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.

Keyword

Carcinoma, non-small-cell lung; Epithelial mesenchymal transition; Immunohistochemistry

MeSH Terms

Adenocarcinoma
Anoxia
Cadherins
Carbon
Carbonic Anhydrases
Carcinoma, Non-Small-Cell Lung
Epithelial-Mesenchymal Transition
Humans
Immunohistochemistry
Lung
Proteins
Cadherins
Carbon
Carbonic Anhydrases
Proteins
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