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Background and Objectives: Recent studies have reported that vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α 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-1α. In addition, we analyzed the relationship between BRAF^(V600E) mutation and clinicopathological parameters, as well as HIF-1α expression in PTMC. Materials and Methods: We retrospectively selected 225patients with PTMC. Immunohistochemical staining for HIF-1α 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-1α (20.7%) and VEGF (30.2%) was more prominent in PTMCs as compared to normal follicular cells. However, HIF-1α 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-1α(p=0.623) or VEGF (p=0.990). Conclusion: HIF-1α 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-1α or VEGF in PTMCs.

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