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BRAFV600E Mutation in papillary thyroid microcarcinoma as recurrence risk factor

Clinical Thyroidology for the Public


The rate of diagnosis of papillary thyroid cancer has increased markedly in the past 20 years. Up to half of these new diagnoses are small (<1 cm) and are termed microcarcinomas. Despite this increase in thyroid cancer, there has not been a corresponding increase in deaths from thyroid cancer, which is ~0.5% over 10 years. While most patients with papillary thyroid cancer do very well, rarely this cancer can be aggressive. Because of this, it is likely that some cancers are overtreated. Predictors of aggressive cancers are being sought to help decrease this risk for overtreatment. One such predictor may be the presence of a mutation in a common cancer gene (BRAFV600E mutation). This mutation has been shown to be common in larger papillary thyroid cancers that are more aggressive. This study was done to determine if the BRAFV600E mutation can predict recurrence in papillary thyroid microcancer, and therefore help to guide treatment decisions.


Chen Y et al BRAFV600E is correlated with recurrence of papillary thyroid microcarcinoma: a systematic review, multi-institutional primary data analysis, and meta-analysis. Thyroid 2016;26:248-55. Epub January 11, 2016


A large search was done for studies that reviewed the correlations between BRAFV600E and recurrence of papillary thyroid microcancer.

At total of 431 articles were initially screened, but only 4 met criteria for inclusion. These inclusion criteria were papillary thyroid cancer less than 10mm in size, BRAFV600E studies, documentation of clinical remission, and at least 2 years of follow-up. Also, 2 unpublished series were added to the analysis. The sample size of the combined series was 2247 patients (average age of 45-50, 77-88% women) from 6 different datasets of patients. BRAFV600E rate was 40-69% of the patients depending upon the series, with recurrence rates of 10.0% in the BRAF+ group and 4.5% in the BRAF negative group. BRAFV600E mutation status was directly correlated this ~2-fold increase in the rate of recurrence.


This study suggests that the presence of the BRAFV600E mutation is correlated with recurrence or papillary microcancers. If this indeed is true, initial treatment could then be tailored to reduce recurrence in higher risk patients, sparing low risk patients from potential side effects of therapy. Prospective trials from the time of nodule evaluation through long-term follow-up will be helpful in confirming the whether the BRAFV600E mutation analysis can predict cancer recurrence.

— Julie Hallanger Johnson, MD

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Thyroid Cancer:


Papillary microcancer: a papillary thyroid cancer smaller than 1 cm in diameter.

Cancer recurrence: this occurs when the cancer comes back after an initial treatment that was successful in destroying all detectable cancer at some point.

Genes: a molecular unit of heredity of a living organism. Living beings depend on genes, as they code for all proteins and RNA chains that have functions in a cell. Genes hold the information to build and maintain an organism’s cells and pass genetic traits to offspring.

Mutation: A permanent change in one of the genes.

BRAF gene: this is gene that codes for a protein that is involved in a signaling pathway and is important for cell growth. Mutations in the BRAF gene in adults appear to cause cancer.