BRAF V600E mutation in prognostication of papillary thyroid cancer (PTC) recurrence

Abstract

Papillary thyroid cancer (PTC) offers excellent prognosis, however relapse risk or persistent disease is related to ~30%. Currently, attention is paid to the possibility of patient group selection of different risk of unfavorable outcome to match a particular therapeutic approach. Therefore, interest in new prognostic and predictive markers known preoperatively is observed. BRAF V600E mutation is such a marker. Many studies analyzing the prevalence of the mutation and its relationship with other clinicopathological risk factors were reported but with controversial conclusions. The prognostic significance of BRAF mutation was confirmed by some single centre studies, a few meta-analyses and a large multicenter retrospective international study. They confirmed a correlation between the mutation and the risk of recurrence. The strongest argument against using BRAF mutation as an independent prognostic and predictive factor in PTC is its high prevalence (30-80%). At present it seems that BRAF mutation is one of the factors influencing the prognosis and it should be analyzed in correlation with other prognostic factors.The most recent ATA recommendations do not indicate a routine application of BRAF status for initial risk stratification in differentiated thyroid cancer due to a lack of evident confirmation of a direct influence of mutation on the increase in relapse risk. However, ATA demonstrates the continuous risk scale for the relapse risk assessment, considering BRAF and/or TERT status. At present, researchers are working on determining the role of BRAF mutation in patients from a low-risk group and its correlations with others molecular events. Currently, BRAF mutation cannot be used as a single, independent predictive factor. However, its usefulness in the context of other molecular and clinico-pathological risk factors cannot be excluded. They may be used to make modern prognostic scales of relapse risk and be applied to individualized diagnostic and therapeutic strategy for PTC patients.

The Profile of Genetic Mutations in Papillary Thyroid Cancer Detected by Whole Exome Sequencing

“…BRAF is the most common mutation in PTC, and its variations may active the MAPK signal pathway, thus promoting the aggressive progression of PTC [30]. It was reported that the prevalence of BRAF mutations was 30-80% [31]. In the present study, the mutations of BRAF gene were observed in 54.54% PTC cases.…”

Clinicopathological Significance of Overall Frequency of Allelic Loss (OFAL) in Lesions Derived from Thyroid Follicular Cell

“…The high prevalence of thyroid carcinomas ranks this disease in first place among all endocrine malignancies worldwide. The incidence of thyroid carcinoma continues to increase, which may be because better, cheaper, and more available diagnostic methods enable the detection of very small changes [ 1 – 4 ]. However, relevant imaging and fine-needle aspiration biopsy (FNAB) are insufficient for diagnosis, and the final diagnosis is established after surgery in up to one-quarter of cases.…”

Genetyczne podłoże nowotworów tarczycy – wybrane zagadnienia

“…Występowanie mutacji powoduje zmianę konformacji białka skutkującą zablokowanie jej w formie stale aktywnej, co powoduje stałe fosforylowanie i aktywowanie kinazy MAP2K1. Podobnie jak w przypadku mutacji w genach RAS skutkuje to stałym pobudzaniem ścieżki sygnałowej MAPK/Erk, niezależnie od czynników zewnątrzkomórkowych [5,15,17].…”