Increased expression of Vascular Endothelial Growth Factor-C in papillary thyroid carcinoma predicts cervical lymph node metastasis

Abstract

Vascular endothelial growth factor C (VEGF-C), a critical tumor lymphangiogenic factor involved in nodal metastases, is suspected to initiate cervical lymph node metastases in papillary thyroid carcinoma (PTC). The purpose of this study is to investigate the expression pattern of VEGF-C in PTC and examine its correlation with any clinicopathologic features. Paired tissues from PTC (n=39) and benign thyroid nodules (n=20) were analyzed for VEGF-C protein expression level and localization using semi-quantitative Western blot analysis and immunohistochemistry, respectively. VEGF-C expression was detected in 27 of 39 PTC, but only 1 out of 20 nodular hyperplasia specimens (p<0.001). Its expression was higher in tumor compared with adjacent non-tumorous tissues while adjacent non-tumorous tissue in metastatic PTC had a significantly higher VEGF-C expression compared with that of non-metastatic PTC tissues (p=0.011). Positive immunohistochemical staining for VEGF-C was observed in both tumors with and without lymph node metastases but not in sections from benign thyroid disease. VEGF-C expression level in PTC correlated significantly with lymph node metastasis and lymph vessel permeation (p=0.004 and 0.001 respectively). In conclusion, over-expression of VEGF-C protein in PTC may predict cervical lymph node metastases, and increased level of VEGF-C in adjacent non-tumorous tissue of the metastatic PTC was probably involved in the process of intrathyroidal lymphangiogenesis and micro-metastasis.