ECE2009 Poster Presentations Thyroid (117 abstracts)
BRAFV600E mutation and timp-1 hyper-expression in classical variants of papillary thyroid carcinoma (PTC)
Alessandra Bommarito , Elvira Carissimi , Pierina Richiusa , Marco Calogero Amato , Leonardo Russo , Giovanni Zito , Giuseppe Pizzolanti & Carla Giordano
University of Palermo, Palermo, Italy.
BRAFV600E mutation is considered useful in recognizing thyroid cancer aggressiveness or poor prognosis particularly in certain variants of papillary thyroid cancinoma (PTC). A recent meta-analysis identified 12 cancer-versus-non cancer gene candidate as markers of thyroid cancer; among these TIMP-1 (tissue inhibitors of metalloproteinases) was found consistently up-regulated. Our aim was to evaluate BRAFV600E mutation and TIMP-1 expression in 14 PTC classical variants (CV) in comparison to 14 PTC other variants (2 tall-cell, 8 follicular, 4 sclerosant variants; OV). BRAFV600E mutation was detected in 11 (78.6%) CV-PTC and in 3 (21.4%) OV-PTC. Using qRT-PCR TIMP-1 was found significantly hyper-expressed in CV-PTC harbouring BRAFV600E mutation (median 14.3 (interquartile range: 8.2–40)) in comparison to respective normal tissues (1.2 (1–2.2); P=0.004). A significant TIMP-1 hyper-expression was confirmed in all 14 BRAF-mutated PTC (median 22.9 (9.2–89.3)) with respect to 14 wild type PTC (median 6.3 (2–13.8); P=0.024).
The proof-of-principle was assessed in vitro using BCPAP cell line, which harbours BRAFV600E mutation, and was found to hyper-express TIMP-1. When BCPAP cells were transiently transfected with target-specific BRAF-siRNA (MU-A) TIMP-1 was significantly down-regulated. Our data prove that BRAFV600E mutation is strongly associated with TIMP-1 up-regulation in CV-PTC, suggesting their potential invasiveness through the well-known TIMP-1 anti-apoptotic activity.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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