Does Addition ofBRAFV600E Mutation Testing Modify Sensitivity or Specificity of the Afirma Gene Expression Classifier in Cytologically Indeterminate Thyroid Nodules?
| Autor: | Catalin Barbacioru, Virginia A. LiVolsi, Jonathan I. Wilde, Lyssa Friedman, P. Sean Walsh, Richard B. Lanman, Edward Y. Tom, Moraima Pagan, Juan Rosai, Giulia C. Kennedy, Richard T. Kloos, Darya Chudova, Mei Wong, Jessica D. Reynolds |
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| Rok vydání: | 2013 |
| Předmět: |
Proto-Oncogene Proteins B-raf
Thyroid nodules medicine.medical_specialty Pathology endocrine system diseases Endocrinology Diabetes and Metabolism Biopsy Fine-Needle Cytological Techniques DNA Mutational Analysis Clinical Biochemistry Mutation Missense Glutamic Acid Biology medicine.disease_cause Sensitivity and Specificity Biochemistry Diagnosis Differential Endocrinology Internal medicine medicine Humans Genetic Testing Thyroid Nodule neoplasms Genetic testing Mutation medicine.diagnostic_test Gene Expression Profiling Biochemistry (medical) Reproducibility of Results Valine medicine.disease digestive system diseases Gene expression profiling Amino Acid Substitution Mutation testing Differential diagnosis Indeterminate HT29 Cells |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 98:E761-E768 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | 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).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.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.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. |
| Databáze: | OpenAIRE |
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