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

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ÀÌÁ¤Èñ, ¹Ú¿ø¿µ, Á¤¼º¹¬, À̹αâ, ±è¿µ´ë, ½Åµ¿ÈÆ, ÀÌâÈÆ,
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ÀÌÁ¤Èñ ( Lee Jung-Hee ) 
ºÎ»ê´ëÇб³ ÀÇ°ú´ëÇÐ º´¸®Çб³½Ç

¹Ú¿ø¿µ ( Park Won-Young ) 
ºÎ»ê´ëÇб³ ÀÇ°ú´ëÇÐ º´¸®Çб³½Ç
Á¤¼º¹¬ ( Jeong Seong-Muk ) 
ºÎ»ê´ëÇб³ ÀÇ°ú´ëÇÐ º´¸®Çб³½Ç
À̹αâ ( Lee Min-Ki ) 
ºÎ»ê´ëÇб³ ÀÇ°ú´ëÇÐ ³»°úÇб³½Ç
±è¿µ´ë ( Kim Young-Dae ) 
ºÎ»ê´ëÇб³ ÀÇÇÐÀü¹®´ëÇпø ÈäºÎ¿Ü°úÇб³½Ç
½Åµ¿ÈÆ ( Shin Dong-Hoon ) 
ºÎ»ê´ëÇб³ ÀÇ°ú´ëÇÐ º´¸®Çб³½Ç
ÀÌâÈÆ ( Lee Chang-Hun ) 
ºÎ»ê´ëÇб³ ÀÇ°ú´ëÇÐ º´¸®Çб³½Ç

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)-1a, 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-1a, 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-1a 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-1a expression and inversely correlated with E-cadherin, HIF-1a expression was not associated with E-cadherin expression. However, considering the relationship between HIF-1a and TWIST expression, further studies should be performed to demonstrate the role of hypoxia-induced EMT in NSCLC.

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

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