Serum Vascular Endothelial Growth Factor C Correlates With Lymph Node Metastases and High-Risk Tumor Profiles in Papillary Thyroid Carcinoma

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Abstract
Objective: To evaluate the clinical relevance of serum vascular endothelial growth factor (VEGF) and VEGF-C in papillary thyroid carcinoma (PTC). Summary Background Data: VEGF is a potent angiogenic factor promoting tumor angioinvasion and distant metastases, whereas VEGF-C enhances nodal metastases because of its lymphangiogenic effect. Although both tissues VEGF and VEGF-C have been shown to contribute to tumor metastases in PTC, the clinical relevance of serum VEGF (sVEGF) and sVEGF-C remains unknown. Methods: Preoperative serum samples collected from 85 primary PTC patients and 44 control subjects with benign thyroid diseases were measured for sVEGF and sVEGF-C levels. Potential correlations between their serum levels and clinicopathologic features as well as the commonly adopted risk group stratification profiles of the tumors were analyzed. Results: Preoperative sVEGF and sVEGF-C levels of PTC patients were significantly higher compared with those of control subjects (P = 0.001 and P < 0.001, respectively). sVEGF-C level was significantly elevated in older patients, those with extrathyroidal invasion and with lymph node metastases whereas sVEGF level was significantly increased in multifocal tumors. sVEGF-C, but not sVEGF, correlated significantly with high risk tumors in all commonly adopted risk group stratification profiles. An elevated preoperative sVEGF-C level of >7200 pg/mL was shown to be the only independent risk factor for nodal metastases. sVEGF-C levels declined significantly at 3 months after thyroidectomy in PTC but not control patients. Conclusions: sVEGF-C levels in PTC patients correlated significantly with the presence of nodal metastases and advanced tumor stages. Its clinical relevance needs further evaluation.