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

Authors' Affiliations: ¹ Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong and ² Discipline of Pathology, School of Medicine, Griffith University, Gold Coast, Australia

Requests for reprints: Chung-Yau Lo, Division of Endocrine Surgery, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. Phone: 852-2817-2291; Fax: 852-2817-2291; E-mail: cylo{at}hkucc.hku.hk.

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.

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