Expression of Vascular Endothelial Growth Factor and Its Receptors in Thyroid Nodular Hyperplasia and Papillary Thyroid Carcinoma: A Tertiary Health Care Centre Based Study

Abstract

Introduction: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in thyroid cancer. VEGF is known to have high affinity to VEGF receptors such as VEGFR-1 (Flt-1) and VEGFR-2 (KDR). Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and studies showed the increasing incidence of PTC arising in nodular hyperplasia. Targeted therapy on these growth factors and receptors are used in management of both differentiated and undifferentiated thyroid carcinoma. This study aims to determine the expression of VEGF and VEGF receptors (VEGFR) in thyroid nodular hyperplasia and PTC. Methods: A cross-sectional study based on paraffinized archival tissue blocks of 113 nodular hyperplasias and 67 PTC from the thyroidectomy specimens in the year of 2003 to 2014. The tissue sections were then stained by immunohistochemistry for VEGF, VEGFR-1 and VEGFR-2. The lymph node involvement and extrathyroid extension also were determined. Results: The mean age of PTC patients was 44.7±15.8 years and nodular hyperplasia were 42.2±13.6 years. There was a statistical difference of VEGFR-1 (p=0.028) and VEGFR-2 (p=0.003) expression between nodular hyperplasia and PTC. However, no significant difference of VEGF expression (p=0.576) between both diseases. Co-expression of VEGF and VEGFR-1 was significant in both nodular hyperplasia (p=0.016) and PTC (p=0.03), meanwhile no relevant relationship for VEGF and VEGFR-2 expression (p>0.05). No significant association (p>0.05) between lymph node status and extrathyroid extension with age groups, gender, VEGF and VEGFR expression. Conclusions: VEGF, VEGFR-1 and VEGFR-2 showed overexpression in both nodular hyperplasia and PTC. The expression of VEGFR-1 and VEGFR-2 are more significant in PTC with relevant co-expression of VEGF and VEGFR-1. Therefore, the inhibition of VEGFR offers a promising prospect for tumour management in thyroid carcinoma.

VEGFA and NFE2L2 Gene Expression and Regulation by MicroRNAs in Thyroid Papillary Cancer and Colloid Goiter

“…The present study shows that tissues affected by papillary thyroid cancer or colloid goiter, and their respective adjacent tissues present increased expression of VEGFA and NFE2L2, thereby providing evidence that vascularization and oxidative stress are imbalanced in these tissues. Corroborating with our results, earlier studies have shown that the expression of the VEGFA is higher in thyroid cancer, and may be crucial for the development of goiter, since the proliferation of endothelial cells precedes that of thyroid cells [15][16][17][18]. Studies have reported functional defects and increased expression of NFE2L2 in the thyroid.…”

Effect of thyroidectomy on circulating angiogenic cytokines in papillary thyroid carcinoma and benign goiter: Potential for new biomarkers?

“…HGF and FGF are known to be potent mitogens for follicular thyroid cells, and the overexpression of FGF, HGF, and VEGF has been described in both nodular hyperplasia and PTC, in contrast to minimal production in normal thyroid tissue. 19,20 Ang-2 shows high expression in PTC tissues related to clinical staging. 9 In the reported literature, the expression of FGF2 and VEGF-C was found to be greater in PTC tissues than in normal tissues.…”

Thyroid dysfunction related to vascular endothelial growth factor receptor tyrosine kinase inhibitors: A real‐world study based on FAERS

“…3 VEGFR-TKIs are used in the treatment of thyroid cancer, because VEGF plays an essential role in the development and progression of thyroid malignancies. 4,5 However, clinical studies have shown that VEGFR-TKIs can induce adverse drug events (ADE), including thyroid dysfunction. [6][7][8] Thyroid dysfunction includes hyperthyroidism and hypothyroidism, both of which could have serious outcomes, and may warrant discontinuation of VEGFR-TKIs treatment.…”