Effects of Coexistent BRAFV600E and TERT Promoter Mutations on Poor Clinical Outcomes in Papillary Thyroid Cancer: A Meta-Analysis.

Effects of Coexistent BRAFV600E and TERT Promoter Mutations on Poor Clinical Outcomes in Papillary Thyroid Cancer: A Meta-Analysis.

Thyroid. 2017 Feb 09;:

Authors: Moon S, Song YS, Kim YA, Lim JA, Cho SW, Moon JH, Hahn S, Park DJ, Park YJ

Abstract
BACKGROUND: Presence of a TERT promoter mutation has been suggested as a potential prognostic marker for thyroid cancer and a synergistic association with the BRAFV600E mutation has been demonstrated. The aim of this study was to verify the role of this genetic duet in papillary thyroid cancer (PTC).
METHODS: Studies of the association of BRAFV600E and TERT promoter mutations with clinicopathological features, recurrence, or PTC-related mortality were included from PubMed and Embase databases (inception to September 2016).
RESULTS: Thirteen eligible studies incorporating 4347 patients with PTC were included and 283 (median 8.3%) of these patients had coexistent BRAFV600E and TERT promoter mutations. Coexistence of the two mutations were far more strongly associated with high-risk clinicopathological features than either mutation alone, including advanced TNM stage (vs. BRAFV600E, OR, 4.19; 95% CI, 3.07-5.71; vs. TERT, OR, 4.66; 95% CI, 2.67-8.13), extrathyroidal extension (vs. BRAFV600E, OR, 3.1; 95% CI, 2.2-4.37; vs. TERT, OR, 5.66; 95% CI, 3.02-10.6), lymph node metastasis (vs. BRAFV600E, OR 1.59; 95% CI, 1.16-2.17; vs. TERT, OR, 2.03; 95% CI, 1.22-3.38), and distant metastasis (vs. BRAFV600E, OR, 11.76; 95% CI, 5.63-24.58). The coexistence of the mutations showed the highest risk of recurrence (the coexistence vs. no mutations, hazard ratio [HR], 6.60; 95% CI, 3.82-11.40; BRAFV600E vs. no mutations, HR, 1.31; 95% CI, 0.49-3.46; TERT vs. no mutations, HR, 3.38; 95% CI, 0.85-13.35). Moreover, PTC-related mortality was significantly higher with coexistent mutations than in the presence of BRAFV600E alone (HR; 20.07; 95% CI, 8.37-48.09).
CONCLUSIONS: Coexistent BRAFV600E and TERT promoter mutations have a synergistic effect on clinical outcomes in PTC, whereas each mutation alone has a modest effect. Therefore, molecular testing of BRAFV600E and TERT promoter mutations together is useful in assessing risk stratification of PTC.

PMID: 28181854 [PubMed - as supplied by publisher]

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