Coexpressed High Levels of VEGF-C and Active MMP-9 Are Associated With Lymphatic Spreading and Local Invasiveness of Papillary Thyroid Carcinoma

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Objectives: Papillary thyroid carcinoma (PTC) usually has a good prognosis, but some patients develop an aggressive course of the disease, leading to a poor outcome. Vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 9 (MMP-9) have been shown to play roles in tumor progression in various human malignancies.

Methods: We analyzed VEGF-C and active MMP-9 expression profiles in PTC samples using immunohistochemistry and Western blotting.

Results: Immunohistochemistry showed positive staining for VEGF-C and active MMP-9 in 83% and 57% of PTCs, respectively (n = 60), with a positive correlation between their expression levels (Spearman, P < .001). Concomitant high expression of VEGF-C and active MMP-9 correlated with the presence of lymph node metastasis (P  = .005), pT status (P  = .004), pTNM tumor stage (P  = .005), and particularly the degree of tumor infiltration (P < .001, Fisher exact test). Densitometric analysis of Western blot bands confirmed correlation between VEGF-C and active MMP-9 expression (Wilcoxon and Spearman tests) and significant association with the clinicopathologic parameters (Mann-Whitney and Kruskal-Wallis tests).

Conclusions: Association of coexpressed high levels of VEGF-C and active MMP-9 with lymphatic spreading and local invasiveness of PTC suggests their potential usefulness as predictive biomarkers of aggressive PTC behavior.

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