VEGF-C Is a Thyroid Marker of Malignancy Superior to VEGF-A in the Differential Diagnostics of Thyroid Lesions

Abstract

IntroductionThyroid nodular goiter is one of the most common medical conditions affecting even over a half of adult population. The risk of malignancy is rather small but noticeable–estimated by numerous studies to be about 3–10%. The definite differentiation between benign and malignant ones is a vital issue in endocrine practice. The aim of the current study was to assess the expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C on the mRNA level in FNAB washouts in case of benign and malignant thyroid nodules and to evaluate the diagnostic value of these markers of malignancy.Materials and MethodsPatients undergoing fine-needle aspiration biopsy (FNAB) in our department between January 2013 and May 2014 were included. In case of all patients who gave the written consent, after ultrasonography (US) and fine-needle aspiration biopsy (FNAB) performed as routine medical procedure the needle was flushed with RNA Later solution, the washouts were frozen in -80 Celsius degrees. Expression of VEGF-A and VEGF-C and GADPH (reference gene) was assessed in washouts on the mRNA level using the real-time PCR technique. Probes of patients who underwent subsequent thyroidectomy and were diagnosed with differentiated thyroid cancer (DTC; proved by post-surgical histopathology) were analyzed. Similar number of patients with benign cytology were randomly selected to be a control group.ResultsThirty one DTCs and 28 benign thyroid lesions were analyzed. Expression of VEGF-A was insignificantly higher in patients with DTCs (p = 0.13). Expression of VEGF-C was significantly higher in patients with DTC. The relative expression of VEGF-C (in comparison with GAPDH) was 0.0049 for DTCs and 0.00070 for benign lesions, medians – 0.0036 and 0.000024 respectively (p<0.0001).ConclusionsMeasurement of expression VEGF-C on the mRNA level in washouts from FNAB is more useful than more commonly investigated VEGF-A. Measurement of VEGF-C in FNAB washouts do not allow for fully reliable differentiation of benign and malignant thyroid nodules and should be interpreted carefully. Further studies on larger groups are indicated. However, measurement of VEGF-C on mRNA level can bring important information without exposing patient for additional risk and invasive procedures.

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

“…This increase in the expression of the VEGFA gene in goiter may be due to several factors. Increasing endothelial cells is the first step in goiter formation, which exhibits levels of VEGFA expression similar to those observed in some types of thyroid cancer [23][24][25]. It is also worth mentioning that most of the papillary cancer samples analyzed in the present study presented early stages according to the TNM (Classification of Malignant Tumors) classification and that the levels of VEGFA gene expression increased according to the types and stages of tumor [15].…”

Angiogenic and lymphangiogenic profiles in histological variants of papillary thyroid carcinoma

“…Recent results reported by Woliński et al 43 suggested that the measurement of VEGF -C mRNA levels is important to distinguish benign and malignant thyroid lesions. They concluded that VEGF -C expression on the mRNA level is more useful than VEGF -A mRNA expression.…”

Editorial on the Special Issue “Novel Methods of Diagnostics of Thyroid and Parathyroid Lesions”

“…High hopes have been pinned on sonoelastography and the application of artificial intelligence [5]. In addition, molecular studies have become an increasingly useful and available tool in thyroid cancer risk assessment [6,7]. In particular, we hope that the introduction of these methods will allow us to reduce the amount of invasive practices performed unnecessarily in patients with benign nodules.…”