Pro and Anti-Angiogenic Vascular Endothelial Growth Factors Expression in Benign and Malignant Thyroid Lesions

Abstract

Vascular endothelial growth factors are the most powerful molecules related to angiogenesis and lymph angiogenesis stimulation and are frequently associated to a worse prognosis in many malignancies. Currently, anti-angiogenic VEGF-A165b has been described and it have been demonstrated to efficiently block the angiogenic sprout. We sought to investigate the VEGF family members expression involved with angiogenesis (including the anti-angiogenic VEGF-A165b) and lymph angiogenesis. The casuistic was composed by 196 cases. The frequencies of thyroid lesions were: 53 (27%) goitres, 16 (8%) thyroiditis, 9 (5%) follicular adenomas, 84 (43%) papillary carcinomas, and 34 (17%) follicular carcinomas. The immunohistochemical reactions for VEGF-A, VEGF-A165b, VEGF-B, VEGF-C and VEGF-D were performed and semi-quantitatively assessed. We observed a widespread positive immunoexpression of VEGF-A and VEGF-A165b in benign and malignant lesions. None of the benign samples of this casuistic had positive immunoexpression of VEGF-B and only a few positive cases were detected in both papillary and follicular carcinomas. The highest levels of VEGF-C and VEGF-D expression were found in papillary carcinomas. There was a relevant association of VEGF-D and a worst tumoral staging (p=0.004) in papillary carcinomas. We also identified a significant association between VEGF-A and vascular invasion (p=0.049) and patient’s age and an increased expression of VEGF-B (p=0.047) in papillary thyroid carcinomas. No association was found for follicular carcinomas.