TheBRAFV600E mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?

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Abstract

Context

An activating mutation in the gene BRAF has been correlated with poorer prognosis and more aggressive clinical course in papillary thyroid carcinoma (PTC). We therefore hypothesized that the good prognosis, high 5-year disease-free rate and high survival rate of patients with less aggressive papillary thyroid microcarcinoma (pT1aNo-x) would be associated with a lower incidence of the BRAFV600E mutation.

Objectives

To evaluate the frequency of the activating mutation BRAFV600E in low-risk papillary thyroid microcarcinoma (pT1aNo-x at the moment of diagnosis) and the association of the mutation with the clinical outcome in a retrospective analysis.

Study Design

BRAFV600E was characterized in 113 PTC patients diagnosed with pT1aNo-x (one PTC focus with a diameter <1 cm, without lymph node or distant metastases according to IUCC/AJCC TNM staging system 2010). Genotyping was performed on DNA extracted from thyroid tumour tissue using direct capillary sequencing, and allele-specific amplification PCR was used to resolve equivocal results. Retrospective analysis of the clinical course of PTC was then correlated with BRAF status in the primary tumour tissue.

Results

The BRAFV600E mutation was detected in 78 of the 113 pT1aNo-x patients (69·0%). We observed no persistence, locoregional recurrence, lymph node or distant metastases or deaths in the study group during the 12-year study (January 2001 to December 2012).

Conclusions

The presence of the activating BRAFV600E mutation in a significant percentage of papillary thyroid microcarcinoma indicates that further analyses are required to verify its usefulness as a predictor of clinical outcome in PTC. In this study, there was no correlation between BRAF-positive primary focus of papillary microcarcinoma and more aggressive or recurrent disease.

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