HIF-1alpha Expression in BRAF(V600E)-Positive Papillary Thyroid Microcarcinoma.
- Author:
Jung Uee LEE
1
;
Koon Soon KIM
;
Hae Joung SUL
;
Dong Ho LEE
;
Kwan Ju LEE
;
Minho SHONG
;
Young Suk JO
Author Information
1. Department of Pathology, St. Mary's Hospital, The Catholic University of Korea, Korea.
- Publication Type:Original Article
- Keywords:
Thyroid cancer;
papillary;
Proto-oncogene proteins B-raf;
Hypoxia-inducible factor 1;
alpha;
Vascular endothelial growth factor
- MeSH:
Carcinoma;
Carcinoma, Papillary;
Humans;
Hypoxia-Inducible Factor 1;
Proto-Oncogene Proteins B-raf;
Retrospective Studies;
Thyroid Gland;
Thyroid Neoplasms;
Vascular Endothelial Growth Factor A
- From:Journal of Korean Thyroid Association
2011;4(2):102-108
- CountryRepublic of Korea
- Language:English
-
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.
