title: 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.
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.
authors: Institute for the Application of Nuclear Energy - INEP, University of Belgrade, Zemun-Belgrade, Serbia.
authors: Ilona
authors: I
authors: Marečko
authors: Dubravka
authors: D
authors: Cvejić
authors: Svetislav
authors: S
authors: Tatić
authors: Vesna
authors: V
authors: Dragutinović
authors: Ivan
authors: I
authors: Paunović
authors: Svetlana
authors: S
authors: Savin
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000201:enzymology* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis / Q000201:enzymology* / Q000378:metabolism; D002291:Carcinoma, Papillary; D002648:Child; D003937:Diagnosis, Differential; D005333:Fetus / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011804:Quinolines; D012372:ROC Curve; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000201:enzymology* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011804:Quinolines; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C117172:AU 006