Article

Molecular Testing for Somatic Mutations Improves the Accuracy of Thyroid Fine-needle Aspiration Biopsy

Department of Surgery, University of California, San Francisco, CA 94143, USA.
World Journal of Surgery (Impact Factor: 2.35). 11/2010; 34(11):2589-94. DOI: 10.1007/s00268-010-0720-0
Source: PubMed

ABSTRACT Thyroid fine-needle aspiration (FNA) biopsy is indeterminate or suspicious in up to 30% of cases and these patients are commonly subjected to at least a diagnostic hemithyroidectomy. If malignant on histology, a completion thyroidectomy is usually performed, which may be associated with higher morbidity. To determine the clinical utility of genetic testing in thyroid FNA biopsy, we conducted a prospective clinical trial.
Four hundred seventeen patients with 455 thyroid nodules were enrolled and had genetic testing for common somatic mutations (BRAF, NRAS, KRAS) and gene rearrangements (RET/PTC1, RET/PTC3, RAS, TRK1) by PCR and direct sequencing and by nested PCR, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of genetic testing in thyroid FNA biopsy were determined based on the histologic diagnosis.
One hundred twenty-five of 455 thyroid nodule FNA biopsies were indeterminate or suspicious on cytologic examination. Overall, 50 mutations were identified (23 BRAF, 4 RET/PTC1, 2 RET/PTC3, 21 NRAS) in the thyroid FNA biopsies. There were significantly more mutations detected in malignant thyroid nodules than in benign (P = 0.0001). For thyroid FNA biopsies that were indeterminate or suspicious, genetic testing had a sensitivity of 12%, specificity of 98%, PPV of 38%, and NPV of 65%.
Genetic testing for somatic mutations in thyroid FNA biopsy samples is feasible and identifies a subset of malignant thyroid neoplasms that are indeterminate or suspicious on FNA biopsy. Genetic testing for common somatic genetic alterations thus could allow for more definitive initial thyroidectomy in those with positive results.

0 Followers
 · 
150 Views
  • Source
    • "Currently, the application of molecular technologies has focused on genetics for the accurate diagnosis and therapy of cancer. Early and/or late stage types of DTC may also be initiated by point mutations in different proto-oncogenes, such as RET, B-RAF, NTRK1, and K-RAS (Namba et al., 2003; Weier et al., 2009; Kim et al., 2010; Moses et al., 2010; Bales and Chopra, 2011). Epigenetic silencing through aberrant DNA methylation of tumor suppressor genes has been reported in TC (Russo et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic alterations in the global DNA methylation status may be associated with an increased risk of some cancer types in humans. The methylenetetrahydrofolate reductase (MTHFR) gene is involved in folic acid metabolism and plays an essential role in inherited DNA methylation profiles. The common 677 C>T and 1298 A>C polymorphisms in the MTHFR gene cause the production of a thermolabile enzyme with reduced function and, eventually, genomic DNA hypomethylation. The current preliminary study was designed to determine the association between germ-line polymorphism in the MTHFR gene and differentiated thyroid carcinoma (DTC). In the current case-control study of 60 thyroid carcinomas (TC); 45 papillary TC, 9 follicular TC, and 6 DTC of an uncertain malignant potential were examined. Genomic DNA was extracted from peripheral blood with EDTA, genotyped by a multiplex real-time polymerase chain reaction. An elevated 2.33-fold risk was observed for DTC in individuals with the 677TT genotype when compared with the control group (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.03-3.58). Current DTC patients showed similar results as a control group for the 1298 A>C allele. No significant risk was detected for the homozygous 1298CC genotype (CC vs. AA or AC) (OR: 1.30, 95% CI: 0.73-2.29). The current results are supportive of the hypothesis that the homozygous MTHFR 677TT genotype increases the risk factor of developing thyroid cancer, and further large-scale studies are needed to validate this association.
    Genetic Testing and Molecular Biomarkers 04/2012; 16(7):780-4. DOI:10.1089/gtmb.2011.0347 · 1.15 Impact Factor
  • Source
    • "Although the results for BRAF and RET/PTC mutations TABLE 1. Summary of four studies with a panel of mutation analyses First author, year (Ref.) Nikiforov et al., 2009 (40) Moses et al., 2010 (20) Ohori et al., 2010 (41) Cantara et al., 2010 (39) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Fine-needle aspiration biopsy (FNAB) is the most sensitive and specific tool for the differential diagnosis of thyroid malignancy. Some limitations of FNAB can be overcome by the molecular analysis of FNAB. This review analyzes the current state and problems of the molecular analysis of FNAB as well as possible goals for increasing the diagnostic rate, especially in the indeterminate/follicular lesion cytological group. Twenty publications were evaluated for the diagnostic material and assay systems used, the type, and the number of mutations screened. Sensitivity, specificity, and false-negative and false-positive rates were calculated for all publications. Testing for a panel of somatic mutations is most promising to reduce the number of indeterminate FNAB. A mean sensitivity of 63.7% was achieved for indeterminate lesions. However, there is a broad sensitivity range for the investigation of mutations in the indeterminate lesions. Therefore, additional molecular markers should be defined by mRNA and microRNA expression studies and evaluated in FNAB samples of thyroid carcinomas without known somatic mutations, and especially for the many benign nodules in the indeterminate/follicular lesion fine-needle aspiration cytology category. This approach should improve the differential diagnosis of indeterminate/follicular lesion FNAB samples. Testing for a panel of somatic mutations has led to an improvement of sensitivity/specificity for indeterminate/follicular proliferation FNAB samples. Further methodological improvements, standardizations, and further molecular markers should soon lead to a broader application of molecular FNAB cytology for the differential diagnosis of thyroid nodules and to a substantial reduction of diagnostic surgeries.
    The Journal of Clinical Endocrinology and Metabolism 05/2011; 96(7):2016-26. DOI:10.1210/jc.2010-2567 · 6.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The accuracy of cancer detection in thyroid nodules by fine-needle aspiration (FNA) cytology and prognostication of thyroid cancer needs further improvement and can benefit from testing for molecular alterations known to occur in thyroid tumors. Recent studies have demonstrated the feasibility of mutation detection in clinical FNA samples from thyroid nodules and their contribution to improving the diagnostic accuracy of FNA cytology. It appears that molecular testing is most beneficial for thyroid FNA samples with indeterminate cytology, where it can resolve the diagnosis in a significant number of cases. In addition to BRAF mutation, which has been studied most extensively, detection of RAS, RET/PTC, and PAX8/PPARgamma mutations also contribute substantially to cancer diagnosis. Some of these molecular markers, particularly BRAF, can also be used for tumor prognostication. In clinical setting, molecular testing of thyroid FNA samples and surgically removed tumors should utilize a restricted number of techniques that provide high accuracy and specificity of mutation detection. Testing for cancer-specific mutations in thyroid FNA samples and surgically removed tumor tissues increases diagnostic accuracy of FNA cytology and offers better prognostication of thyroid cancer.
    Thyroid: official journal of the American Thyroid Association 11/2009; 19(12):1351-61. DOI:10.1089/thy.2009.0240 · 3.84 Impact Factor
Show more

Preview (2 Sources)

Download
0 Downloads
Available from