Expression of matrix metalloproteinase-2 and its tissue inhibitor-2 in fetal and neoplastic thyroid tissue and their significance as diagnostic and prognostic markers in papillary carcinoma

Article type: Research Article

Authors: Mareĉko, Ilona^a | Cvejić, Dubravka^a | Tatić, Svetislav^b | Dragutinović, Vesna^c | Paunović, Ivan^{d; e} | Savin, Svetlana^{a; *}

Affiliations: [a] Institute for the Application of Nuclear Energy – INEP, University of Belgrade, Zemun-Belgrade, Serbia | [b] Institute of Pathology, School of Medicine, University of Belgrade, Belgrade, Serbia | [c] Institute of Medical Chemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia | [d] Center for Endocrine Surgery, Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia | [e] School of Medicine, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia

Correspondence: [*] Corresponding author: Dr. Svetlana Savin, Institute for the Application of Nuclear Energy – INEP, University of Belgrade, Banatska 31b, P.O.Box 46, 11080 Zemun – Belgrade, Serbia. Tel.: +381 11 2618 666; Fax: +381 11 2618 724; E-mail: [email protected].

Abstract: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have roles in physiological and pathological processes. We evaluated immunohistochemical expression of MMP-2 and TIMP-2 in paraffin sections of 12 human fetal thyroids at mid-term gestation and 79 thyroid tumors of follicular origin. Besides evaluating expression of these proteins during fetal development and neoplastic transformation, we determined whether expression of MMP-2 and TIMP-2 may help to differentiate papillary thyroid carcinoma (PTC) from follicular thyroid adenoma (FTA) and/or peritumoral tissue (PT). We also investigated their relationship with prognostically important clinicopathological parameters of PTC. Immunoreactive MMP-2 and TIMP-2 were found in all fetal thyroid tissues examined. Tumor tissues contained variable amounts of MMP-2 and TIMP-2, with overexpression of these proteins in PTC compared to FTA and PT tissue. According to the statistical analysis, MMP-2 distinguished follicular variant of PTC from FTA and overall PTC from total nonmalignant lesions. In PTC, high MMP-2 expression correlated with lymph node metastasis (P=0.022), while high TIMP-2 expression was positively correlated with tumor size (P=0.049) and extrathyroid invasion (P=0.017). Overall, these results indicate a role for MMP-2 and TIMP-2 in both thyroid development and malignant transformation and suggest that positive immunohistochemistry for MMP-2 and TIMP-2 might support diagnosis of PTC and predict unfavorable biological behavior.

Keywords: Human fetal thyroid, papillary thyroid carcinoma, matrix metalloproteinase-2, tissue inhibitors of matrix metalloproteinase-2, immunohistochemistry, clinico-pathological parameters

DOI: 10.3233/CBM-2012-0258

Journal: Cancer Biomarkers, vol. 11, no. 1, pp. 49-58, 2012