Does Addition of BRAF V600E Mutation Testing Modify Sensitivity or Specificity of the Afirma Gene Expression Classifier in Cytologically Indeterminate Thyroid Nodules?

作者：Kloos Richard T; Reynolds Jessica D; Walsh P Sean; Wilde Jonathan I; Tom Edward Y; Pagan Moraima; Barbacioru Catalin; Chudova Darya I; Wong Mei; Friedman Lyssa; LiVolsi Virginia A; Rosai Juan; Lanman Richard B; Kennedy Giulia C^*

来源：Journal of Clinical Endocrinology & Metabolism, 2013, 98(4): E761-E768.

DOI：10.1210/jc.2012-3762

Objective: The purpose of this study was to determine the frequency of BRAF mutation in cytologically indeterminate thyroid nodules and to investigate whether adding the BRAF test improves diagnostic accuracy of the Afirma Gene Expression Classifier (GEC).
Design: BRAF V600E mutational status was determined for DNA extracted from cytologically benign (n = 40), indeterminate (n = 208), and malignant (n = 48) fine-needle aspiration specimens previously categorized by GEC as molecularly Benign or Suspicious. Analytical performance of the BRAF assay was assessed to establish reproducibility and limits of detection. Molecular testing results were correlated with blinded expert histopathological diagnoses.
Results: The BRAF assay detected mutations reproducibly to 2.5% mutant allele frequency. The prevalence of BRAF mutations in cytologically benign specimens was 2 of 40 (5.0%, 95% confidence interval [CI], 0-16) and in cytologically malignant specimens was 36 of 48 (75.0%, 95% CI, 60-86). In the cytologically indeterminate category, 10.1% of specimens were BRAF+: 2 of 95 were subcategorized as atypia of undetermined significance or follicular lesion of undetermined significance (2.1%, 95% CI, 0-7); 1 of 70 as follicular neoplasm or suspicious for follicular neoplasm(1.4%, 95% CI, 0-9); and 18 of 43 as suspicious for malignancy (41.9%, 95% CI, 27-58). All BRAF+ specimens were classified as Suspicious by the GEC.
Conclusions: BRAF mutations are uncommon in nodules with atypia of undetermined significance or follicular lesion of undetermined significance or follicular neoplasm or suspicious for follicular neoplasm cytology. Most cytologically indeterminate nodules that proved to be malignant were also BRAF-, and all nodules that were false-negative by GEC were also BRAF-. Similarly, all BRAF+ specimens were also GEC Suspicious. Neither GEC test sensitivity nor specificity was improved by addition of BRAF mutation testing. (J Clin Endocrinol Metab 98: E761-E768, 2013)

• 出版日期2013-4