Preoperative plasma concentrations of vascular endothelial growth factor and matrix metalloproteinase 9 are associated with stage progression in papillary thyroid cancer

OBJECTIVE Vascular endothelial growth factor (VEGF), a potent angiogenic peptide, and matrix metalloproteinase 9 (MMP-9), a proteolytic enzyme, are found to be abundantly expressed in several types of cancer and correlate with tumour progression. In this study, we investigated the relationship between preoperative plasma VEGF, MMP-9 levels and disease stages in papillary thyroid cancer. DESIGN Plasma samples were consecutively collected from 30 patients with papillary thyroid cancer preoperatively (seven males and 23 females with a mean age of 45 +/- 16 years) and control plasmas obtained from 30 patients with benign goitre (seven males and 23 females with a mean age of 44 +/- 18 years) and 23 healthy persons (four males and 19 females with a mean age 44 +/- 15 years). Plasma VEGF and MMP-9 concentrations were determined by enzyme-linked immunosorbent assay. Cancer progression was staged by the TNM classification of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC). RESULTS In thyroid cancer patients, the plasma VEGF and MMP-9 values were higher than those in controls (51.8 +/- 11.5 ng/l vs. 27.0 +/- 0.8 ng/l; 72.3 +/- 23.3 mug/l vs. 22.1 +/- 3.0 mug/l, respectively; P < 0.05), and those in benign goitre (51.8 +/- 11.5 ng/l vs. 39.7 +/- 8.8 ng/l; 72.3 +/- 23.3 mug/l vs. 23.0 +/- 2.2 mug/l, respectively; P < 0.05). But, there was no difference of plasma VEGF and MMP-9 between patients with goitre and normal subjects. A comparison of VEGF and MMP-9 levels in patients at each cancer stage and in patients with benign nodule found that plasma VEGF and MMP-9 values in TNM stages III and IV, but not stage I or II, were significantly elevated (P < 0.05). When cancer patients were grouped according to clinopathological features, the plasma VEGF and MMP-9 concentrations were both significantly elevated in patients with large tumour size (P < 0.01), lymph node involvement (P < 0.01), extrathyroidal invasion (P < 0.05), distant metastasis (P < 0.05) or advanced stages (P < 0.01). CONCLUSION Our study demonstrated that circulating VEGF and MMP-9 levels correlated with progression of papillary thyroid cancer, suggesting plasma VEGF and MMP-9 may serve as preoperative adjuvant markers for assessing disease activity in papillary thyroid cancer. However, they should not be used as a diagnostic tool for differentiating malignant from benign thyroid disorders.