Coexpressed High Levels of VEGF-C and Active MMP-9 Are Associated With Lymphatic Spreading and Local Invasiveness of Papillary Thyroid Carcinoma.
OBJECTIVE
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.
From the Institute for the Application of Nuclear Energy-INEP.
Sonja
S
Šelemetjev
From the Institute for the Application of Nuclear Energy-INEP.
Ilona
I
Ðoric
Center for Endocrine Surgery, Institute for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia.
Ivan
I
Paunovic
Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade-Zemun, Serbia.
Svetislav
S
Tatic
From the Institute for the Application of Nuclear Energy-INEP.
Dubravka
D
Cvejic
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
D014408:Biomarkers, Tumor; D042582:Vascular Endothelial Growth Factor C; D020780:Matrix Metalloproteinase 9
Matrix metalloproteinase 9; Papillary thyroid carcinoma; Prognostic biomarkers; Vascular endothelial growth factor C