J Korean Thyroid Assoc.
2011 Nov;4(2):102-108.
HIF-1alpha Expression in BRAF(V600E)-Positive Papillary Thyroid Microcarcinoma
- Affiliations
-
- 1Department of Pathology, St. Mary's Hospital, The Catholic University of Korea, Korea.
- 2Research Center for Endocrine and Metabolic Diseases, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea. ysmrj@cnuh.co.kr, minhos@cnu.ac.kr
- 3Department of Surgery, St. Mary's Hospital, The Catholic University of Korea, Korea.
Abstract
- BACKGROUND AND OBJECTIVES
Recent studies have reported that vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha are up-regulated in BRAF(V600E)-positive papillary thyroid carcinoma (PTC). We investigated whether papillary thyroid microcarcinomas (PTMCs) also exhibited increased expression of VEGF and HIF-1alpha. In addition, we analyzed the relationship between BRAF(V600E) mutation and clinicopathological parameters, as well as HIF-1alpha expression in PTMC.
MATERIALS AND METHODS
We retrospectively selected 225 patients with PTMC. Immunohistochemical staining for HIF-1alpha and VEGF was performed using paraffinembedded PTMC tissue microarrays. BRAF(V600E) 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-1alpha (20.7%) and VEGF (30.2%) was more prominent in PTMCs as compared to normal follicular cells. However, HIF-1alpha and VEGF expression was not correlated with clinicopathological features. BRAF(V600E) mutation was found in 70.7% (159/225) of the PTMC cases. PTMCs harboring the BRAF(V600E) mutation exhibited larger tumor sizes as compared to PTMCs without the BRAF(V600E) mutation (p=0.038). However, BRAF(V600E) mutation status did not correlate with the expression of HIF-1alpha (p=0.623) or VEGF (p=0.990).
CONCLUSION
HIF-1alpha and VEGF were more frequently detected in PTMCs as compared to normal thyroid tissues. However, BRAF(V600E) mutation status was not correlated with the expression of HIF-1alpha or VEGF in PTMCs.
Keyword
MeSH Terms
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Carcinoma
Carcinoma, Papillary
Humans
Hypoxia-Inducible Factor 1
Proto-Oncogene Proteins B-raf
Retrospective Studies
Thyroid Gland
Thyroid Neoplasms
Vascular Endothelial Growth Factor A
Carcinoma
Carcinoma, Papillary
Hypoxia-Inducible Factor 1
Proto-Oncogene Proteins B-raf
Thyroid Neoplasms
Vascular Endothelial Growth Factor A
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