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KMID : 1202020110040020102
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Journal of Korean Thyroid Association
2011 Volume.4 No. 2 p.102 ~ p.108
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HIF-1? Expression in BRAFV600E-Positive Papillary Thyroid Microcarcinoma
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Lee Jung-Uee
Kim Koon-Soon
Sul Hae-Joung
Lee Dong-Ho
Lee Kwan-Ju
Shong Min-Ho
Jo Young-Suk
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Abstract
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Background and Objectives : Recent studies have reported that vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1? are up-regulated in BRAFV600E-positive papillary thyroid carcinoma (PTC). We investigated whether papillary thyroid microcarcinomas (PTMCs) also exhibited increased expression of VEGF and HIF-1?. In addition, we analyzed the relationship between BRAFV600E mutation and clinicopathological parameters, as well as HIF-1? expression in PTMC.
Materials and Methods : We retrospectively selected 225 patients with PTMC. Immunohistochemical staining for HIF-1? and VEGF was performed using paraffin- embedded PTMC tissue microarrays. BRAFV600E mutation status was analyzed by dideoxy sequencing.
Results: PTMCs larger than 0.5 cm tend to be related to aggressive clinicopathological features such as thyroid capsular invasion (p=0.023) and bilaterality (p=0.047). Immunoreactivity to HIF-1? (20.7%) and VEGF (30.2%) was more prominent in PTMCs as compared to normal follicular cells. However, HIF-1? and VEGF expression was not correlated with clinicopathological features. BRAFV600E mutation was found in 70.7% (159/225) of the PTMC cases. PTMCs harboring the BRAFV600E mutation exhibited larger tumor sizes as compared to PTMCs without the BRAFV600E mutation (p=0.038). However, BRAFV600E mutation status did not correlate with the expression of HIF-1? (p=0.623) or VEGF (p=0.990).
Conclusion: HIF-1? and VEGF were more frequently detected in PTMCs as compared to normal thyroid tissues. However, BRAFV600E mutation status was not correlated with the expression of HIF-1? or VEGF in PTMCs.
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KEYWORD
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Thyroid cancer, papillary, Proto-oncogene proteins B-raf, Hypoxia-inducible factor 1, alpha, Vascular endothelial growth factor
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