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Concomitant high expression of survivin and vascular endothelial growth factor-C is strongly associated with metastatic status of lymph nodes in papillary thyroid carcinoma

1 Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Serbia
2 Center for Endocrine Surgery, Institute for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Serbia
3 Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia

Correspondence Address:
Dubravka Cvejic,
Institute for the Application of Nuclear Energy INEP, 11080 Zemun, Belgrade, Banatska 31b, Serbia

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Source of Support: None, Conflict of Interest: None

Purpose: Papillary thyroid carcinoma (PTC) has a strong propensity to metastasize to regional lymph nodes which increases the risk of local-regional relapse and affects the course of the disease. Molecular pathogenesis of lymph node metastasis (LNM) is not yet fully understood. Survivin, a multifunctionale molecule involved in apoptosis, proliferation and angiogenesis, and vascular endothelial growth factor-C (VEGF-C) are suggested to be implicated in lymphatic metastases of human malignancies. Materials and Methods: Expression of survivin and VEGF-C was examined by immunohistochemistry and Western blot in 75 cases of PTCs in relation to their LNM status. Additionally, survivin and VEGF-C were immunohistochemically analyzed in 15 primary PTCs paired with their metastatic tissue in lymph nodes. Results: High expression of survivin and VEGF-C was found in 62.7% and 64.0% cases, respectively, with a positive correlation to each other (Spearman's correlation co-efficient = 0.878, P < 0.001). Expression levels of both proteins were significantly higher in patients with LNM than in those without LNM (P < 0.001). The rate of concomitant high expression of survivin and VEGF-C in patients with LNM involvement was 88.9% (P < 0.01). Metastatic tissue in lymph nodes expressed survivin and VEGF-C at the same high extent as their primary tumors. Conclusion: Concomitant high expression of survivin and VEGF-C is closely associated with LNM status of PTC patients, which suggests their cooperation in the metastatic process. Evaluation of survivin and VEGF-C expression could be clinically significant in predicting the metastatic potential of PTC and subsequent treatment and follow-up of these patients.

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