Prognostic utility of BRAF mutation in papillary thyroid cancer

Abstract

Papillary thyroid cancer (PTC) is a common endocrine malignancy that frequently harbors the oncogenic T1799A BRAF mutation. As a novel prognostic molecular marker, this mutation has received considerable attention in recent years for its potential utility in the risk stratification and management of PTC. In PTC, BRAF mutation is closely associated with extrathyroidal extension, lymph node metastasis, advanced tumor stages, disease recurrence, and even patient mortality. Many of the responsible molecular derangements promoted by, or associated with, BRAF mutation have been identified, including over-expression of tumor-promoting genes, suppression of tumorsuppressor genes, and silencing of thyroid iodide-handling genes, resulting in impairment or loss of radioiodine avidity and hence the failure of radioiodine treatment of PTC. BRAF mutation can be readily tested for on thyroid fine needle aspiration biopsy specimens, with high preoperative predictive probabilities for clinicopathological outcomes of PTC. As such, knowledge of BRAF mutation status can facilitate more accurate risk stratification and better decision making at various steps in the management of PTC, from preoperative planning of initial surgical scale to postoperative decisions about appropriate radioiodine treatment and thyroid-stimulating hormone suppression, and to selections of appropriate surveillance modalities for PTC recurrence. The greatest utility of BRAF mutation status is in those cases where traditional clinicopathological criteria alone would otherwise be unreliable in the risk stratification and management of PTC. Use of this unique molecular marker, in conjunction with conventional clinicopathological risk factors, to assist the prognostication of PTC is likely to improve the efficiency of contemporary management of thyroid cancer.

Surgical Perspective of T1799A BRAF Mutation Diagnostic Value in Papillary Thyroid Carcinoma

“…Some studies support these findings with a prevalence average of 45% (Xing, 2005;2009;Nikiforova and Nikiforov, 2009). …”

“…In thyroid cancer, molecular test is used to enhanced diagnosis and give an additional information that would affect prognosis. T1799A BRAF mutation is a molecular marker that is specific for PTC (Xing, 2007;2009;Nikiforova and Nikiforov, 2009). In this study, we tested the role of BRAF mutation to solve our preoperative diagnostic problems.…”

“…Solid variant of PTC also has a different type of mutation which is associated with RET/PTC3 rearrangement (Knauf et al, 2005;Nikiforova and Nikiforov, 2009). Although BRAF mutation as a diagnostic test is specific for PTC, there are studies that stated its limitation as a diagnostic tool because of its low sensitivity (Xing, 2007;2009) There are some studies evaluated BRAF mutation diagnostic value. Zatelli et al (2009) found sensitivity of 64% and Sapio et al (2007) found sensitivity of 37.5% from specimens of inconclusive cytology.…”

An update on molecular biology of thyroid cancers

“…The BRAF point mutation is the most common mutation in PTC (35-70%) and has recently been reported to be associated with poor prognostic features like extrathyroidal soft tissue infiltration, lymph node metastasis, disease aggressiveness, tumor recurrence, loss of radioiodine avidity and, thus, resistance to annual therapeutic methods [29][30][31][32][33][34]199,200]. Additionally, the BRAF mutation occurs most commonly in aggressive subtypes of PTC [178,201].…”

RAC1b overexpression in papillary thyroid carcinoma: a role to unravel

“…The V600E mutation constitutively activates BRAF kinase, leading to prolonged stimulation of the MAPK pathway, which ultimately leads to uncontrolled cell proliferation and faulty apoptosis (8,9,12). The majority of studies have associated BRAF V600E mutation with a more aggressive PTC behavior, whereas a few studies failed to reproduce this finding (13,14,15,16,17,18,19,20,21,22). Still, its value as a prognostic marker remains incompletely established and other players might be implicated, justifying the search for additional molecular markers.…”