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Endocrine Abstracts (2015) 37 EP1142 | DOI: 10.1530/endoabs.37.EP1142

1Department of Molecular Bases of Medicine, I Chair of Internal Medicine, Medical University of Lodz, Lodz, Poland; 2Department of Endocrine, General and Vascular Surgery, Chair of Endocrinology, Medical University of Lodz, Lodz, Poland.


The search for new differentiating biomarkers in follicular-cell derived thyroid tumors (FCDT), especially for the FNAB with underdetermined cytology, is an important scientific task. Disturbed expression of tumor suppressor genes plays important role in thyroid carcinogenesis. In this study we focused on epigenetic mechanism influencing on trefoil factor 3 (TFF3) and tissue inhibitor of metalloproteinases 3 (TIMP3) expression.

Aim of the study: Evaluation of TFF3 and TIMP3 promoter hypermethylation and gene expression as candidate biomarkers in differentiating diagnosis of FCDT neoplasms.

Material: Thyroid neoplasms and matching macroscopically unchanged tissues (control) from 86 patients with preoperative FNAB diagnosis: ‘follicular neoplasm’/PTC. Final diagnosis: FA (n=9), PTC (n=35), FTC (n=9) and NG (n=33).

Methods: DNA bisulfite conversion, followed by promoter methylation level evaluation in methylation specific PCR, Methylation Index (MI) calculation. mRNA expression level (RQ) measured by real-time PCR using Low Density Arrays. The results (MI, RQ) were correlated with the clinicopathological features.

Results: TIMP3 MI value correlates with RQ (P=0.029) and increase with patients age. TIMP3 MI and RQ are higher in woman vs men (P=0.016). TIMP3 MI value was significantly higher in follicular lesions (FTC/FA), than in NG and PTC (P=0.049). TIMP3 expression was the highest in FA, the lowest in FTC, RQ values don’t correlate with methylation pattern. TFF3 MI value revealed the opposite correlation to TIMP3 – low MI in FTC/FA. In PTC TFF3 MI correlates with RQ level (P=0.01). The significant correlations among TIMP3 and TFF3 MI levels and among their expressions were observed (P=0.00008 for MIs, P=0.00 for RQs). In women positive correlation between MIs and RQs for TIMP3 and TFF3 were found (P=0.0004, P=0.00 resp.). RQ values regarding pTNM groups reversely correlate with MI for both genes (P>0).

Conclusions: The increased TIMP3 MI values in FA/FTC, and TFF3 in PTC suggest that can be regarded as promising biomarkers for FCDT distinguishing. Our research indicates that simultaneous analysis of methylation profile and expression level of TIMP3 and TFF3 may be diagnostically useful. Further studies are needed.

Disclosure: This work was financially supported by the Polish Ministry of Science and Higher Education (Iuventus Plus programme, 2012–2015, grant No. 0082/IP1/2011/71).

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