BRAF Mutation Analysis in Fine Needle Aspiration (FNA) Cytology of the Thyroid

Jin, Long; Sebo, Thomas J.; Nakamura, Nobuki; Qian, Xiang; Oliveira, André M.; Majerus, Julie A.; Johnson, Michele R.; Lloyd, Ricardo V.

doi:10.1097/01.pdm.0000213461.53021.84

Cited by 134 publications

(89 citation statements)

References 31 publications

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“…As reported by Jin et al 35 for BRAF p.V600E mutation, the choice of four different approaches (direct sequencing, the colorimetric TrimGen Mutector assay, PCR with FRET probes, and PCR with SYBR Green) does not significantly affect the molecular diagnosis, and the choice of the best test depends mainly on the laboratory expertise and available financial and technical resources.…”

Section: Discussionmentioning

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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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: Discussionmentioning

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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“…Polymerase chain reaction and direct forward and reverse sequencing of the BRAF gene were performed on formalin-fixed paraffinembedded tissue as described previously. 19,24,25 …”

Section: Methodsmentioning

confidence: 99%

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

et al. 2011

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The majority of papillary thyroid carcinoma is indolent and associated with long-term survival. The columnar cell variant, however, is a rare subtype that is variable in biological behavior; some are clinically aggressive, whereas others are more clinically indolent. Tumor size, tumor circumscription, and encapsulation may influence the behavior of columnar cell carcinomas. Other variables including genetic changes and putative biomarkers associated with malignant growth have not been thoroughly examined in these neoplasms. In this study, nine cases of columnar cell variant of papillary thyroid carcinoma from three institutions were classified as clinically indolent or aggressive based on pathological features, clinical history, and outcome. Indolent tumors were typically small, circumscribed or encapsulated, and from younger female patients, whereas aggressive tumors were large, locally aggressive, associated with regional and distant metastasis, and from older male patients. The missense mutation, V600E in the BRAF oncogene (BRAF V600E ), was detected in three of nine of cases, of which two were clinically aggressive. Immunohistochemical evaluation of neoplasiaassociated markers showed increased nuclear cyclin D1 expression, elevated Ki-67 proliferation indices, and predominantly weak nuclear p53 staining in both indolent and aggressive tumors. Expression of b-catenin was largely restricted to a membranous pattern in both tumor types. Cytoplasmic expression of bcl-2 was overall mildly reduced in indolent neoplasms. Nuclear expression of estrogen and progesterone receptors was increased in both indolent and aggressive neoplasms, but was without sex-or age-related differences; however, whereas progesterone receptor expression was diffuse and strong in clinically indolent carcinomas, its expression was diminished in aggressive neoplasms. Recognition of the clinicopathological characteristics and the molecular and immunophenotypic features of the columnar cell variant of papillary thyroid carcinoma may aid in characterizing neoplasms that behave indolently or aggressively. Keywords: BRAF (BRAF V600E ); b-catenin; columnar cell variant; cyclin D1; papillary thyroid carcinoma Papillary thyroid carcinoma is a common endocrine neoplasm that is typically indolent and associated with long-term survival. This favorable biological behavior reflects the vast majority of conventional and histological variants of well-differentiated papillary thyroid carcinoma. However, a more aggressive tumoral growth characterizes a small subset that behaves more akin to poorly differentiated and undifferentiated thyroid carcinoma. Initially included in this group of aggressive neoplasms, the columnar cell variant is a rare subtype with variable biological behavior. Early reports described tumors with fast growth rates, aggressive local invasion, high rates of recurrence, early metastasis to regional lymph nodes and distant

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“…This variability may have introduced inconsistencies in the results of BRAF mutation testing. Although we performed BRAF mutation analysis with both FNAB specimens and surgical specimens, numerous studies have demonstrated that BRAF mutation analysis can be performed readily and reliably using solely FNAB specimens preoperatively (Chung et al 2006, Jin et al 2006). In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT.…”

Section: Discussionmentioning

confidence: 99%

Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma

Kim¹,

Woo²,

Lee³

et al. 2015

Endocrine-Related Cancer

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It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (ORZ0.662, PZ0.023) and BRAF-positive (ORZ0.817, PZ0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (ORZ0.675, PZ0.044) and BRAF-positive (ORZ0.817, PZ0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status. Key Words" BRAF mutation " papillary thyroid carcinoma " chronic lymphocytic thyroiditis " central lymph node metastasis " extrathyroidal extension

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BRAF Mutation Analysis in Fine Needle Aspiration (FNA) Cytology of the Thyroid

Cited by 134 publications

References 31 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

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma

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