The Expression And Significance Of Hypoxia-inducible Factor-1Α, Metallothionein, Snail And E-cadherin In Papillary Thyroid Carcinoma

Abstract Objective To investigate the significance of Hypoxia-induciblefactor-1α （HIF-1α）, Metallothionein （MT）, Snail and E-cadherinexpression in patients with papillary thyroid carcinoma （PTC）.Methods91thyroidectomy specimens including12nodular goitersand79PTC were performed using immunochemistry to analyze MT,HIF-1α and Snail expression. After treated with hypoxia (5%O2) for12h,MT, Snail and E-cadherin were detected by Western blotting. The mRNAlevel of HIF-1α, MT, Snail and E-cadherin were detected by RT-PCR. Theivasion and migration were detected by transwell.Results Positive expression of MT, HIF-1α and Snail was shown in56.96%,92.41%and53.16%of PTC, respectively. The positive expressionof MT, HIF-1α andSnail in PTC was associated with lymph-nodemetastasis （p=0.0002, p=0.0056and p=0.0376, respectively）as well asTNM stage （p<0.0001, p=0.0079and p<0.0001, respectively）. Positiveexpression of MT was significantly correlated with that of Snail （r=0.38850, p=0.0004） and that of HIF-1α （r=0.22626, p=0.0450）,while a significant correlation was showed between HIF-1α and Snail（r=0.37145, p=0.0008）. After treated with hypoxia (5%O2) for12h, theprotein and mRNA expression levels of HIF-1α, MT, Snail increased, andthe expression level of E-cadherin was just the opposite.Conclusion Co-expression of HIF-1α, MT, Snail and E-cadherin suggestsnot only an early marker of tumor cells metastasis, but also a significantprognostic predictor in patient with PTC.