Increased Expression of Vascular Endothelial Growth Factor C in Papillary Thyroid Carcinoma Correlates with Cervical Lymph Node Metastases

Abstract

Purpose: Despite recent studies showing that vascular endothelial growth factor C (VEGF-C) mRNA is up-regulated in papillary thyroid carcinoma (PTC), the role of VEGF-C in lymph node metastasis is still unclear. The aim of this study is to investigate the expression pattern of VEGF-C immunoreactive protein in PTC and its relationship with cervical lymph node metastasis. Experimental Design: Tissue samples were obtained from 39 specimens of PTC (20 with and 19 without lymph node metastasis) as well as 20 benign thyroid nodules. Overexpression of the VEGF-C protein was evaluated by immunoblotting with specific anti-VEGF-C antibody in paired tumor and nontumor tissues from PTC. The data were compared with patients' clinicopathologic features and lymph node metastasis. Immunohistochemical staining was done on selected paraffin sections to determine cellular localization of VEGF-C and to assess flt-4 (or VEGFR-3)–positive vessel density in PTC lesions. Results: Overexpression of VEGF-C was detected in 69% of the PTC and in 5% of the benign thyroid specimens. When comparing between the metastatic and nonmetastatic groups of PTC, a higher expression level of VEGF-C was detected in both the tumor (P = 0.004) and adjacent nontumor tissues (P = 0.011). Positive immunostaining for VEGF-C was confirmed in PTC tumor tissues and metastatic lymph nodes, which correlated with flt-4-positive vessel density in tumor and peritumor tissues. The increased expression of VEGF-C protein in PTC is associated with lymph node metastasis (P = 0.004) and lymphovascular permeation (P = 0.001) but is independent of other clinicopatholgic variables. Conclusions: The VEGF-C immunoreactive protein is overexpressed in PTC lesions, which correlates with lymph node metastases. VEGF-C expression may play a role in lymphangiogenesis of PTC and further study is necessary to evaluate the clinical application of VEGF-C as a molecular marker for tumor metastases to cervical lymph nodes.

Telomerase inhibition strategies by siRNAs against either hTR or hTERT in oral squamous cell carcinoma

“…22 VEGF is highly expressed in many human cancers. 23 Its expression is positively related to angiogenesis. The tumor sections of nude mice displayed significant carcinoma necrosis in the tumor masses (visible by both naked-eye observation and immunochemistry detection), which corresponded to the decreased expression of VEGF.…”

“…The protein expression of vascular endothelial growth factor (VEGF), which served as a marker of angiogenesis, was measured by immunohistochemistry using a VEGF antibody (Santa Cruz, Santa Cruz, CA). 17 Statistics and data analysis All the experiments were performed in triplicate except the animal experiment (n ¼ 5). All of the data are expressed as mean ± s.d.…”

A Radiation-Induced Gene Signature Distinguishes Post-Chernobyl from Sporadic Papillary Thyroid Cancers

“…Increased serum concentrations of VEGF-A and EGFR protein were also reported in PTC (36,39), eventually inducing systemic effects. It is interesting to note that increased levels were especially linked with PTC characterized by lymph node metastases and more aggressive behavior (40) and patients over the age of 45 (41). Again, post-Chernobyl PTC appeared more aggressive at presentation with lymph node metastasis (60-80%); other extrathyroidal spread and venous invasion were commonly observed (11)(12)(13).…”

New perspectives on the treatment of differentiated thyroid cancer

“…Studies have demonstrated that VEGFR is overexpressed in thyroid cancer (41) and VEGF-C immunoreactive protein is correlated with papillary lymph node metastases (42). Serum VEGF is significantly elevated in patients with papillary thyroid cancer compared with the control group (43), especially in patients with metastatic differentiated thyroid cancer but not in those with poorly differentiated thyroid cancer metastases (44).…”