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The Korean Journal of Pathology 2010;44(5): 469-476.
doi: https://doi.org/10.4132/KoreanJPathol.2010.44.5.469
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.
Jung Hee Lee, Won Young Park, Seong Muk Jeong, Min Ki Lee, Young Dae Kim, Dong Hoon Shin, Chang Hun Lee
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.
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.
Key Words: Carcinoma, non-small-cell lung; Epithelial mesenchymal transition; Immunohistochemistry
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