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.

Keywords: VEGF; VEGFR-1; VEGFR-2; thyroid nodular hyperplasia; papillary thyroid carcinoma.

Figure 1

Strong expression of VEGF in cytoplasm of thyrocytes of nodular hyperplasia. Original magnification x 400.

Figure 2

Immunohistochemical Detection of VEGFR-1 in Cytoplasm and Membrane (Red Arrow) of Papillary Thyroid Carcinoma Cells (A) and cytoplasm of thyrocytes of nodular hyperplasia (B). Green arrows indicate VEGFR-1 staining in endothelial lining of blood vessels. Original magnifications, A, x 400 and B, x 100.

Figure 3

Immunohistochemical Detection of VEGFR-2 in Cytoplasm of Papillary Thyroid Carcinoma Cells (A) and cytoplasm of thyrocytes of nodular hyperplasia (B). Original magnifications, A, x 400 and B, x 100.