Overexpression of EphB4, EphrinB2, and EGFR in Papillary Thyroid Carcinoma

Abstract

Objectives: 1) Analyze the expression of EphB4, EphrinB2 and epidermal growth factor receptor (EGFR) in papillary thyroid carcinoma (PTC). 2) Analyze the association of each of these biomarkers with lymph node disease. Methods: Twenty one patients with newly diagnosed PTC (stages I-III) were enrolled in this study between 2009-2012. All 21 patients were treated with total thyroidectomy and central (level VI) neck dissection. EphB4, EphrinB2 and EGFR expression in tumor and surrounding normal thyroid tissue was evaluated by complimentary DNA (cDNA) microarray (n = 4), Western blot (n = 21) and immunohistochemistry (IHC) (n = 21). Clinicopathologic data (tumor size, histologic extension, lymph node disease, stage) was collected from patient records. Results: cDNA microarray analysis showed a statistically significant average fold change in gene expression for EphB4 (2.5, P = .004), EphrinB2 (2.4, P = .001) and EGFR (2.9, P = .003) in tumor samples compared to normal tissue. Linear regression analysis of IHC integrated optical density (IOD) measurements confirmed overexpression of EphB4 ( P < .001), EphrinB2 ( P < .001) and EGFR ( P < .001) in tumor versus benign tissue. We noted an association between lymph node disease and EphB4 ( P < .001), EphrinB2 ( P < .001) and EGFR ( P = .069) expression in tumor samples. Conclusions: Overexpression of EphB4, EphrinB2 and EGFR is associated with PTC. Our results are the first to demonstrate the association between EphB4, EphrinB2 and EGFR overexpression with lymph node metastases in PTC. These three genes may be used as biomarkers for early identification of lymph node involvement in PTC and potential small-molecule targets for future research in PTC pharmacotherapy.