Molecular Profile and Clinical-Pathologic Features of the Follicular Variant of Papillary Thyroid Carcinoma

Zhu, Zhaowen; Gandhi, Manoj; Nikiforova, Marina N.; Fischer, Andrew H.

doi:10.1309/nd8d9lajtrctg6qd

Cited by 347 publications

(214 citation statements)

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“…While in PTC, RAS mutations were observed in approximately 10% of cases, in ATC and FTC this frequency is 10-20% and 40-50%, respectively [90][91][92][93]. RAS mutation in PTC leads follicular variants, and also more encapsulation, and fewer metastases to lymph node [94,95]. In ATCs, RAS mutations are generally observed in tumors that develop microfollicular pattern [96].…”

Section: Rasmentioning

confidence: 99%

An update on molecular biology of thyroid cancers

Ömür

Baran

2014

Critical Reviews in Oncology/Hematology

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Section: Rasmentioning

confidence: 99%

An update on molecular biology of thyroid cancers

Ömür

Baran

2014

Critical Reviews in Oncology/Hematology

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“…19 Mutations in the family of RAS oncogenes, which encode for G-proteins that also convey signals to the MAPK pathway, are more common in follicular carcinomas (FTC) 20 and in follicular variant of papillary carcinoma (fvPTC). 21 Point mutations in the HRAS, KRAS, and NRAS genes are associated with specific domains of the protein and are able either to increase its affinity for substrate (substitution in residues 12 and 13) or to inactivate the autocatalytic GTPase function (residue 61). RAS mutations seem to be related to benign as well as malignant growth of nodules; however, it is becoming evident that alterations in this family of oncogenes are competent to lead toward anomalous cellular transformation, through mechanisms of genomic instability 22,23 and promotion of additional mutations.…”

mentioning

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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“…Thyroid carcinomas may express mutated forms of all three ras (H-ras, K-ras and N-ras) genes (Nikiforova et al, 2003b). Ras mutations are infrequent in PTC, where they are restricted to aggressive PTC subtypes (Garcia-Rostan et al, 2003), and to the follicular PTC variant (Zhu et al, 2003). Between 20 and 50% of FTC are positive for ras mutations (Tallini, 2002).…”

mentioning

confidence: 99%

“…Between 20 and 50% of FTC are positive for ras mutations (Tallini, 2002). The N-ras mutation in codon 61 is the most frequent ras mutation in FTC and it is more frequent in malignant than in benign thyroid tumors (Motoi et al, 2000;Garcia-Rostan et al, 2003;Nikiforova et al, 2003b;Vasko et al, 2003;Zhu et al, 2003).…”

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confidence: 99%

Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas

et al. 2006

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Ras oncogenes are frequently mutated in thyroid carcinomas. To verify the role played by N-ras in thyroid carcinogenesis, we generated transgenic mice in which a human N-ras(Gln61Lys) oncogene (Tg-N-ras) was expressed in the thyroid follicular cells. Tg-N-ras mice developed thyroid follicular neoplasms; 11% developed follicular adenomas and B40% developed invasive follicular carcinomas, in some cases with a mixed papillary/ follicular morphology. About 25% of the Tg-N-ras carcinomas displayed large, poorly differentiated areas, featuring vascular invasion and forming lung, bone or liver distant metastases. N-ras(Gln61Lys) expression in cultured PC Cl 3 thyrocytes induced thyroid-stimulating hormone-independent proliferation and genomic instability with micronuclei formation and centrosome amplification. These findings support the notion that mutated ras oncogenes could be able to drive the formation of thyroid tumors that can progress to poorly differentiated, metastatic carcinomas.

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Molecular Profile and Clinical-Pathologic Features of the Follicular Variant of Papillary Thyroid Carcinoma

Cited by 347 publications

References 0 publications

An update on molecular biology of thyroid cancers

An update on molecular biology of thyroid cancers

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

Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas

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