Molecular Testing for Mutations in Improving the Fine-Needle Aspiration Diagnosis of Thyroid Nodules

Nikiforov, Yuri E.; Steward, David L.; Robinson-Smith, Toni M.; Haugen, Bryan R.; Klopper, Joshua; Zhu, Zhaowen; Fagin, James A.; Falciglia, Mercedes; Weber, Katherine; Nikiforova, Marina N.

doi:10.1210/jc.2009-0247

Cited by 652 publications

(623 citation statements)

References 38 publications

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“…10,12 Moreover, we detected 10/48 mutated samples (21%) with a higher incidence of RAS variants in comparison with previous reports in Thy 3 patients. 10,16 In addition to establishing the evident advantages of HRM prescreening in terms of time and economic improvement, this pilot study confirmed the accuracy of the proposed method. Complete concordance was found between the standard protocol, based on sequencing of all samples, and the HRM-based screening.…”

Section: Discussionsupporting

confidence: 61%

“…The screening of chromosomal rearrangements (RET/ PTC1, RET/PTC3, and PAX8/PPARG) was developed using primer sets reported by Nikiforov et al 16 Amplification reactions were performed in simplex assay on a 7900HT fast real-time PCR system (Applied Biosystems-Life Technologies) using 2.5 L of cDNA in a total volume of 12.5 L containing a final concentration of 1ϫ QuantiTect SYBR Green from a PCR kit (Qiagen) and 300 nmol/L of each primer. PCR was performed as follows: an initial hold at 95°C for 15 minutes, followed by 45 two-step cycles at 95°C for 15 seconds and 60°C for 60 seconds.…”

Section: Amplification Conditions For Chromosomal Rearrangement Screementioning

confidence: 99%

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A High-Resolution Melting Protocol for Rapid and Accurate Differential Diagnosis of Thyroid Nodules

Mancini

Pinzani

Pupilli

et al. 2012

The Journal of Molecular Diagnostics

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Thyroid cancer is the most common malignancy of the endocrine system, accounting for approximately 1% of all malignancies in Western countries. 1 The incidence of thyroid cancer has increased 2.6-fold in the last 30 years. This change is attributed not only to an increment in papillary thyroid carcinoma, 2 but also to more wisely conducted medical surveillance and improvements in diagnostic tools. 3 The large majority of thyroid nodules, as discovered with the use of new diagnostic imaging techniques, are asymptomatic and benign. In this context, diagnostic studies are becoming essential to identify the small fraction of thyroid nodules that harbor malignant disease and to predict when surgery is indicated. Fine-needle aspiration biopsy (FNAB) has emerged over the past 30 years as an accurate and cost-effective procedure for the preoperative screening of thyroid nodules, representing the gold standard for differential diagnosis of benign and malignant nodules. 4 Under recent guidelines, 5,6 cytological smears are classified in five categories for the diagnostic report: Thy 1, nondiagnostic; Thy 2, benign or negative for malignant cells; Thy 3, all follicular lesions (including atypia/ follicular lesion of undetermined significance and follicular neoplasm or suspicious for follicular neoplasm); Thy 4, suspicious; and Thy 5, diagnostic for malignancy.Although the overall accuracy of FNAB is considered excellent, approximately 30% of cytological aspirates do not allow definitive diagnosis of malignancy, because of intrinsic and unavoidable characteristics of samples. 7 The major limitations of FNAB procedures are linked to inadequate and indeterminate specimens and, in that sense, are also linked respectively to the nondiagnostic or follicular lesions categories. 8,9 Thus, a clinical need emerges for the characterization of aspirates with suspicious features but with unsatisfactory cellularity, to allow accurate distinction of benign from malignant forms of follicular lesions.Several somatic mutations have been identified in thyroid cancer, stimulating the search for genetic alterations in FNAB that could increase the diagnostic accuracy of traditional cytology. Numerous studies have demonstrated that identification of specific mutations in cytological specimens can assist in the diagnosis by FNAB and in the clinical decision to excise the nodule and to intensify the follow-up. 10 -16 In most cases, genetic alterations are represented by activating mutations of oncogenes that are mutually exclusive and linked to distinct histological subtypes, with a demonstrated pathogenic role in thyroid cell transformation as effectors of the RAS/RAF/ MAPK signaling cascade.The presence of BRAF mutations, a frequent alteration in papillary carcinoma (PTC), evolves into an unregulated activation of the intracellular MAPK pathway that can promote tumorigenesis and tumor progression. The main mutation of BRAF, identified exclusively in PTC, affects

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Section: Discussionsupporting

confidence: 61%

Section: Amplification Conditions For Chromosomal Rearrangement Screementioning

confidence: 99%

A High-Resolution Melting Protocol for Rapid and Accurate Differential Diagnosis of Thyroid Nodules

Mancini

Pinzani

Pupilli

et al. 2012

The Journal of Molecular Diagnostics

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“…Most studies demonstrated that the sensitivity of molecular assays has improved by combined detection of BRAF and RET/PTC. An increased sensitivity from about 42.3-69% to 56.4-78% has been reported [196][197][198].…”

Section: Molecular Targets In Histopathological Diagnosis and Classifmentioning

confidence: 91%

“…TRK rearrangements may also be added to this panel. Presence of BRAF, RAS, RET/PTC, PAX8-PPAR␥ and TRK in FNAB samples correlated with malignancy in 97% of cases [196,197,212]. Therefore, detection of any mutation of this panel is a strong predictor for thyroid cancer.…”

Section: Molecular Targets In Histopathological Diagnosis and Classifmentioning

confidence: 98%

An update on molecular biology of thyroid cancers

Ömür

Baran

2014

Critical Reviews in Oncology/Hematology

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“…11,12 With regard to papillary thyroid carcinomas, evidence suggests that molecular testing for BRAFV600E in thyroid fineneedle aspirations can be a useful tool to separate this malignancy from other thyroid nodules. 13 The mutation status also serves as a prognostic marker as its presence is associated with higher rates of tumor recurrence and mortality. 14 In the case of colorectal carcinomas, BRAFV600E mutation positive patients have significantly shorter progression-free survival when compared with patients with tumors with BRAF wild-type and its presence is shown to impair the therapeutic effect of drugs such as cetuximab and panitumumab.…”

mentioning

confidence: 99%

Immunohistochemistry with a mutation-specific monoclonal antibody as a screening tool for the BRAFV600E mutational status in primary cutaneous malignant melanoma

2013

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The V600E mutation of BRAF has emerged as both an effective biomarker and therapeutic target for select benign and malignant cutaneous and non-cutaneous human tumors and is typically determined using DNAbased techniques that include allele-specific PCR and direct DNA sequencing. Recently however, the development of new antibodies directed against the V600E protein has opened the door for an easier and more efficient strategy for identifying this mutation. Our present aim was to determine the efficacy of one such antibody, anti-B-Raf (V600E), a mouse monoclonal antibody in which the immunogen is a synthetic peptide derived from the internal region of BRAFV600E. A total of 35 cases of primary cutaneous melanoma were evaluated using a combination of DNA-based techniques that included allele-specific PCR and/or direct DNA sequencing and immunohistochemistry. Cases of papillary thyroid carcinomas (n ¼ 5) and colorectal carcinomas (n ¼ 5), known to harbor the BRAFV600E mutation, served as positive controls for the study. DNA analyses revealed that 6 of 35 (17%) cases of the primary cutaneous malignant melanoma possessed the BRAFV600E mutation. For immunohistochemical analyses, cytoplasmic positivity with anti-B-Raf was noted in 7 of 35 (20%) cases of primary melanoma and in all 10 positive controls. Statistical analyses of the data demonstrated that the sensitivity of the immunohistochemistry was 100% and specificity was 97%. Findings from the current study support the potential use of immunohistochemistry as an ancillary screening tool to assess the BRAFV600E mutation status in primary cutaneous melanoma.

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Molecular Testing for Mutations in Improving the Fine-Needle Aspiration Diagnosis of Thyroid Nodules

Abstract: These results indicate that molecular testing of thyroid nodules for a panel of mutations can be effectively performed in a clinical setting. It enhances the accuracy of FNA cytology and is of particular value for thyroid nodules with indeterminate cytology.

Cited by 652 publications

References 38 publications

A High-Resolution Melting Protocol for Rapid and Accurate Differential Diagnosis of Thyroid Nodules

A High-Resolution Melting Protocol for Rapid and Accurate Differential Diagnosis of Thyroid Nodules

An update on molecular biology of thyroid cancers

Immunohistochemistry with a mutation-specific monoclonal antibody as a screening tool for the BRAFV600E mutational status in primary cutaneous malignant melanoma

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