Relationship between Protein Expression of VEGF-C, MMP-2 and Lymph Node Metastasis in Papillary Thyroid Cancer

Abstract

Papillary thyroid cancer (PTC) is a common malignancy and has a good prognosis after appropriate treatment. PTC cells spread mainly by lymph node metastasis (LNM), but the mechanism is not well understood. Expression of vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 2 (MMP-2) protein was studied immunohistochemically from the archived specimens of 65 PTC patients who initially presented without LNM. In this retrospective study, the frequency of expression differed significantly between thyroid cancer tissue and adjacent normal follicular epithelium (VEGF-C 78.5% and 20.0%, respectively; MMP-2 81.5% and 36.7%, respectively). LNM developed in 35 of the patients during 5 - 15 years of follow-up, by the end of which the frequencies of expression of VEGF-C and MMP-2 protein expression were 91.4% and 94.3%, respectively. Both VEGF-C and MMP-2 protein expression were significantly more frequent in PTC with LNM than without LNM. VEGF-C and MMP-2 protein expression levels were significantly correlated with LNM and it is, therefore, feasible that VEGF-C and MMP-2 may be useful as tumour markers of PTC with cervical LNM.

VEGFR1 expression is related to lymph node metastasis and serum VEGF may be a marker of progression in the follow-up of patients with differentiated thyroid carcinoma

“…VEGF-C and VEGF-D have previously been shown to be related to lymph node metastasis in patients with DTC (18)(19)(20)(21). Although lymphangiogenesis is thought to be mediated by VEGFR-3, this study demonstrated a relation between the expression of VEGFR1 and lymph node metastasis in DTC.…”

The Wnt/β-catenin pathway drives increased cyclin D1 levels in lymph node metastasis in papillary thyroid cancer

“…However, these markers do not appear to discriminate between PTC with and without nodal metastases. In the small body of work examining metastatic PTC disease, 2 small cohorts demonstrated that vascular endothelial growth factor-C (VEGF-C), metallomatrix proteinase 2, and basic fibroblast growth factor (bFGF) were expressed more frequently in PTC primary tumors with nodal metastases, but the nodal deposits were not surveyed [27,28]. Previous studies examining cell cycle markers in benign, malignant, and metastatic thyroid neoplasms demonstrated that cyclin D1, cyclin E1, p16, p21, and p27 were expressed at higher levels in PTC primary tumors [11,27].…”

Insidious role of nitric oxide in migration/invasion of colon cancer cells by upregulating MMP-2/9 via activation of cGMP-PKG-ERK signaling pathways

“…This increase in VEGF mRNA may serve as an adaptive response to the reduced oxygen availability. Increased VEGF expression will promote angiogenesis in tumors and facilitate tumor aggressiveness and metastasis [58][59][60].…”