Abstract

Vascular endothelial growth factors (VEGFs) are a family of proteins involved in several elements that play an important role in the development of blood vessels. Besides acting in angiogenesis, VEGFA has important roles in chemotaxis, for macrophages and granulocytes, and vasodilation. VEGFA binds to VEGFR2, that acts on the MAPK and PI3K pathways, fundamental pathways for thyroid carcinogenesis. In order to assess the expression of VEGFA and VEGFR2, in different thyroid nodules, we used a Tissue MicroArray including 91 benign (74 females, 16 males, 49.84±12.65years old) and 125 malignant thyroid nodules (97 females, 28 males, 46.57±14.87 years old). Clinical and pathology data were obtained from 47 goiters; 43 follicular adenomas (FA) and a total of 104 papillary thyroid carcinomas (PTC), including 35 classic papillary thyroid carcinomas (CPTC), 30 follicular variant of PTC (FVPTC), 25 oxifilic variant of PTC (OVPTC), 14 tall cell papillary thyroid carcinomas (TCPTC); and 21 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 116.9±70.8 months. VEGFA protein expression did not differentiate benign from malignant thyroid nodules. However, VEGFA was more frequently expressed in the less differentiated thyroid tissues. In fact, 95.8% of the FTC had positive expression. On the contrary, the intensity of this protein expression was progressively lower according to the process of cellular dedifferentiation (Goiter: 21.4%; FA: 16.3%; PTC: 8.7% and FTC: 0.0%; x2 = 0.031). There was no difference in VEGFR2 expression between malignant and benign nodules (x2= 0.108), but this protein showed more intense expression in tissues that also presented Hürthle cells (x2 <0.0001). We were not able to find any correlation, neither of VEGFA nor with VEGFR2 expression, and any other feature of aggressiveness, including invasion, metastasis, lymph node metastasis, and distant metastasis. We conclude that VEGFA and VEGFR2 expression may help identify less differentiated tumors and the analysis of a larger cohort may prove the clinical utility of these markers.

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