Endocrine Abstracts (2017) 49 EP1406 | DOI: 10.1530/endoabs.49.EP1406

Association of TIMP-3 expression and BRAF V600E mutation status in papillary thyroid cancer

Maryam Zarkesh1, Mehdi Hedayati1, Azita Zadeh-Vakili1, Afsoon Daneshafrooz1, S Adeleh Razavi1, S-Ahmad Fanaei2, Forough Foroughi3 & Fereidoun Azizi4


1Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Association Professor of General Surgery, Erfan Hospital, Tehran, Iran; 3Department of Pathology, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran.


Background: The aim of this study was to assess the association between tissue inhibitor of metalloproteinase-3 (TIMP-3) gene expression and B-Raf Proto-Oncogene (BRAF) V600E mutation in marginal and tumoral tissues of papillary thyroid carcinoma (PTC) patients.

Methods: Sixty fresh frozen tissues of PTC including 55.3% women were collected during thyroidectomy surgery. All clinicopathologic features of subjects were collected which confirmed by a pathologist. The exon 15 of BRAF gene was genotyped by sequencing, TIMP-3 gene expression was assessed using SYBR-Green Real-Time PCR, and the protein level of TIMP-3 was measured using ELISA.

Results: The mean age in men and women was 39.6±15.6 and 37.5±11.6 years, respectively. BRAF mutant was found in 24 (31.6%) of PTC samples. The mean of TIMP-3 mRNA level was higher in marginal tissue compare to tumoral ones (P> 0.05). However, the mean of protein level of TIMP-3 was significantly higher in marginal tissue compare to tumoral (P=0.001). Moreover, in subjects with BRAF positive mutation, the mean of TIMP-3 gene expression was higher in marginal compare to tumoral tissues (P=0.066). On the other hand, in subjects without BRAF mutation, the mean of TIMP-3 protein level was significantly lower in tumoral tissues compare to marginal tissue (P=0.003). However, this difference was not significant in subjects with negative BRAF mutation (P=0.084).

Conclusion: This study showed that although the gene expression of TIMP-3 was marginally different in two BRAF positive and negative mutation groups, it was significantly different in protein levels.

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