Is There a Clinical or Diagnostic Utility for BRAF V600E Mutation in Thyroid Lesions?
C Deng, YL Liu, J Knezetic, Z Gatalica. Creighton University, Omaha, NE; Allegheny General Hospital, Pittsburgh, PA
Background: Thyroid carcinoma develops as a consequence of accumulation of molecular genetic changes in the follicular cells, characteristically involving RET/PTC and B-RAF mutations. Although the V600E point mutation in the BRAF oncogene was reported in papillary thyroid carcinoma (PTC), the sensitivity and specificity of the BRAF mutation in various thyroid carcinomas have not been fully investigated. In addition, if the BRAF mutation is sensitive and specific for PTC, it could be a helpful tool in diagnosing difficult cases.
Design: Sixty four cases of resected thyroid lesions included papillary carcinoma (34), follicular adenoma (n=10), follicular carcinoma (n=6), Hashimotos thyroiditis (6), medullary carcinoma (4), C-cell hyperplasia (1), nodular hyperplasia/goiter (2), and lymphoma (1) were examined for this study. The lesions were microdissceted from the surrounding non-lesional thyroid tissue; total genomic DNA was purified and amplified using specific primers that flanked the BRAF mutation. The PCR product was purified and subsequently sequenced in both directions using the same primer set and an ABI 3100-Avant system to identify the codon mutation at amino acid 600 of the BRAF gene.
Results: Eleven out of 34 (32.4%) PTC contained the V600E BRAF mutation, including 7 conventional PTC, 2 follicular variant PTC and 2 papillary microcarcinomas. The mutation was only observed in the carcinoma cells; not in the surrounding normal tissue. The mutation was not associated with gender, age, or the size of the lesion. The average tumor size was 2.1 1.2 cm in the mutant group and 1.5 1.2 cm in the wild type (WT) group (p=0.233). The average age was 51.5 15.8 (range 32 to 77) years and 48.5 10.8 (range 26 to 67) years in the mutant and WT groups, respectively (p=0.57). Both mutant and WT groups had very few cases with cervical lymph node metastasis for meaningful evaluation. No other lesion harbored the mutation at the V600E locus of the BRAF gene.
Conclusions: The V600E mutation of the BRAF gene is specifically involved in the carcinogenesis of PTC (100% specificity) but was detected in a minority of the cases (32.4% sensitivity). The BRAFV600E mutation is not associated with the tumor size and patients' age and sex, therefore limiting its usefulness in prognosis of PTC. No BRAF mutation was detected in any other lesions which may be helpful in differential diagnoses of an atypical thyroid aspiration in a setting of thyroid nodular lesions.
Tuesday, March 10, 2009 9:15 AM
Platform Session: Section G 1, Tuesday Morning