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

摘要

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