Introduction: Although overall accuracy of fine needle aspiration (FNA) in identifying thyroid cancer is considered excellent, 2030% of aspirates do not allow definitive diagnosis of malignancy. Proto-oncogene somatic mutations such as BRAFV600E in FNA strongly suggest the presence of malignancy. However, only few studies reported the use of circulating BRAFV600E-mutated alleles in plasma as an useful marker for non invasive diagnosis and follow up of this disease.
Methods: We propose an allele specific Taqman-based real-time PCR assay to measure plasma-circulating BRAFV600E concentration in patients affected by thyroid nodules (n=100) and healthy subjects (n=33) used as control group.
Results: Plasma-circulating BRAFV600E concentration (ng/ml) was significantly higher in the cytological categories of follicular lesions (Thy 3; n=47, mean±S.E.M: 2.2±0.9, P=0.04) and suspicious plus diagnostic for malignancy (Thy 4+Thy 5; n=29 mean±S.E.M: 1.7±0.5, P=0.01) than in control group (mean±S.E.M: 0.3±0.1). Plasma-circulating BRAFV600E levels in patients with negative for malignancy cytology (Thy 2 group; n=27 mean±S.E.M: 0.8±0.4, P=0.6) were not significantly different compared to control subjects.
In 18 subjects affected by differentiated thyroid carcinoma the level of circulating BRAFV600E decreased significantly after surgery (from 3.1±0.8 to 0.8±0.3 ng/ml, P=0.02).
ROC curve analysis indicated that BRAFV600E absolute concentration has the maximal diagnostic relevance with 76% sensitivity and 82% specificity.
At present all the patients with Thy 3 cytology are submitted to surgery. In this group, the comparison of the BRAFV600E status with the histological examination demonstrated a negative predictive value of 73%.
Conclusions: The present results suggest that circulating BRAFV600E might be used in the diagnosis of differentiated thyroid cancer. It may be also helpful in the follow-up of these type of cancer, especially in the cases in which thyroglobulin (Tg) is not informative, i.e when antiTg antibodies are present, preoperatively Tg is undetectable and patients were not subjected to radioablation.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
05 - 09 May 2012
European Society of Endocrinology