Reduced tissue inhibitor of metalloproteinase‑2 expression is associated with advanced medullary thyroid carcinoma

Wajner,Simone Magagnin; Capp,Clarissa; Brasil,Beatriz Assis; Meurer,Luise; Maia,Ana Luiza

doi:10.3892/ol.2013.1767

Reduced tissue inhibitor of metalloproteinase‑2 expression is associated with advanced medullary thyroid carcinoma

Authors:
- Simone Magagnin Wajner
- Clarissa Capp
- Beatriz Assis Brasil
- Luise Meurer
- Ana Luiza Maia
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Affiliations: Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035‑003, Brazil, Department of Pathology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035‑003, Brazil
Published online on: December 19, 2013 https://doi.org/10.3892/ol.2013.1767
Pages: 731-737

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Abstract

Matrix metalloproteinases (MMPs) are enzymes for extracellular matrix remodeling that are involved in tumor growth, progression and metastasis. Among them, MMP‑9 has been implicated in tumor angiogenesis. Tissue inhibitor of matrix metalloproteinase (TIMP)‑2, a member of the family of MMP inhibitors, induces apoptosis and inhibits various stages of angiogenesis. Previous studies analyzing the expression of MMP‑9 and TIMP‑2 in medullary thyroid carcinoma (MTC) are scarce. The aims of the current study were to evaluate MMP‑9 and TIMP‑2 expression in MTC samples and correlate the results with clinical parameters. Paraffin‑embedded samples from 77 MTC patients were evaluated for expression by immunohistochemistry. The clinical data in medical records were retrospectively reviewed. In total, 77 patients aged 35.6±17.1 years were enrolled. Of these patients, 36 had hereditary disease (46.8%). Immunohistochemical staining for MMP‑9 and TIMP‑2 was detected in 89.6 and 93.5% of the samples, respectively. The expression of MMP‑9 was not found to correlate with clinical parameters, although, a trend toward a correlation between MMP‑9 and distant metastasis was observed (P=0.053). By contrast, TIMP‑2 staining was found to correlate with age at diagnosis (P=0.026) and negatively correlate with tumor size and tumoral stage (P=0.002 and P=0.001, respectively). Notably, the highest levels of TIMP‑2 expression were observed in patients with intrathyroidal disease. The MMP‑9 enzyme involved in extracellular matrix remodeling is overexpressed in MTC lesions and may contribute to tumor vascularization and growth. Reduced levels of TIMP‑2 expression may be implicated in tumor progression and spread of disease.

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