Coexpressed high levels of VEGF-C and active MMP-9 are associated with lymphatic spreading and local invasiveness of papillary thyroid carcinoma

Abstract

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. © American Society for Clinical Pathology, 2016. All rights reserved.