MMP-9-1562 C/T single nucleotide polymorphism associates with increased MMP-9 level and activity during papillary thyroid carcinoma progression.

Autor: Roncevic J; Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Belgrade, Serbia., Djoric I; Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Belgrade, Serbia., Selemetjev S; Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Belgrade, Serbia., Jankovic J; Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Belgrade, Serbia., Dencic TI; Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Belgrade, Serbia., Bozic V; Clinical Centre of Serbia, Department of Endocrine and Cardiovascular Pathology, Belgrade, Serbia., Cvejic D; Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Belgrade, Serbia. Electronic address: dubravka@inep.co.rs.
Jazyk: angličtina
Zdroj: Pathology [Pathology] 2019 Jan; Vol. 51 (1), pp. 55-61. Date of Electronic Publication: 2018 Nov 27.
DOI: 10.1016/j.pathol.2018.10.008
Abstrakt: Papillary thyroid carcinoma (PTC), a common form of thyroid malignancy, displays significant variations in clinical features and outcome. The malignant transformation of the thyroid is driven by altered expression of many matrix-modulating enzymes, including matrix metalloproteinase-9 (MMP-9). A single nucleotide polymorphism in its promotor (-1562 C/T) is suspected to cause overexpression of MMP-9, which in turn contributes to development of a tumour unfavourable phenotype. The aim of this study was to investigate the impact of MMP-9 promotor genotype on MMP-9 expression in PTC samples, and to assess its value as a possible risk factor for developing PTC or its aggressive phenotype. A total of 105 PTC patients and 43 healthy controls were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In order to estimate MMP-9 expression, PTC tissue sections were stained immunohistochemically. Statistical analysis showed that PTC cases and controls did not differ significantly in genotype frequencies (OR = 2.27, CI = 0.854-6.022). In PTC samples, the presence of the T allele was accompanied by elevated MMP-9 expression (p = 0.047) as well as a higher risk of developing extrathyroid extensions (p = 0.037) and high TNM stages (p = 0.009). Moreover, we observed overexpression of MMP-9 in cases presenting with extrathyroid invasion (p = 0.001), lymph node metastasis (p = 0.028), large tumour size (p = 0.031) and advanced stage (p = 0.005) compared to indolent tumours, along with enhanced enzymatic activity demonstrated by in situ zymography. Data suggests that MMP-9 (-1562 C/T) does not facilitate predisposition for PTC but affects the disease course by modulating MMP-9 expression. Genotyping MMP-9 provides important information which may prove beneficial in risk stratification of PTC patients.
(Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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