Analysis of BRAFV600E Mutation Status in Papillary Thyroid Carcinoma with Single or Multiple Tumor Nodules
Josenia NM Tan, Antonio de las Morenas, Shi Yang, Huihong Xu. Boston University Medical Center, Boston, MA
Background: The advent of molecular studies has refined the approach to the diagnosis, prognosis and treatment of cancers. In papillary thyroid carcinoma (PTC), BRAF mutation is reported to be the most prevalent genetic alteration particularly the BRAFV600E that has been correlated with more aggressive behavior. Patients diagnosed with PTC often present with multifocal tumors with a predominant nodule measuring >1cm or multiple microcarcinomas. It has been previously proposed that this is the result of intraglandular metastasis arising from a single tumor. However, recent molecular studies support the independent clonal origin of these tumors. Furthermore, the uncertainty of how microcarcinomas behave has also been questioned with the reported prevalence of BRAFV600E mutation in these tumors. The purpose of this study is to determine the BRAFV600E status in multifocal nodules when this mutation in the predominant nodule is absent.
Design: A retrospective review of the BRAFV600E mutation of cases with a diagnosis of PTC between 08/2011 and 09/2012 was performed. All multicentric tumors with absent BRAFV600E mutation in the dominant nodule were reviewed and an additional tumor focus was submitted for BRAF assay with standard diagnostic allelle-specific PCR.
Results: A total of 64 cases were included in this study. Thirty-three (33) cases had single nodules, among which 16 had BRAFV600E mutation. Among the 31 cases with multiple tumor foci, 17 had BRAFV600E mutation in the predominant nodule. The remaining 14 cases without BRAFV600E mutation in the predominant nodule, 3 additional tumor foci were found to have this mutation.
|Mean size, cm (range)|
|PTC variant||No. of cases||Gender, F||Mean age, years (range)||Single tumor n=33||Multifocal n=31||BRAF v600E mutation by variant|
|Dominant tumor||Additional foci|
|BRAF v600E mutation by tumor focality|