<i>RET</i> rearrangements and <i>BRAF</i> mutation in undifferentiated thyroid carcinomas having papillary carcinoma components

Mochizuki, Kazuki; Kondo, Tetsuo; Nakazawa, Tadao; Iwashina, Masanori; Kawasaki, Tomonori; Nakamura, Nobuki; Yamane, Tetsu; Murata, Shin Ichi; Ito, Koichi; Kameyama, Kaori; Kobayashi, Makio; Katoh, Ryohei

doi:10.1111/j.1365-2559.2010.03646.x

Cited by 36 publications

(24 citation statements)

References 37 publications

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“…The RET/PTC rearrangement has been investigated in many studies. No RET/PTC arrangement was detected in benign lesions such as nodular hyperplasias and follicular adenomas in our study, as was the case with most of the studies in the literature (8,27,48).…”

Section: Discussionsupporting

confidence: 67%

BRAFV600E Mutation, RET/PTC1 and PAX8-PPAR Gamma Rearrangements in Follicular Epithelium Derived Thyroid Lesions - Institutional Experience and Literature Review

Şahpaz¹,

Önal²,

Yeşilyurt³

et al. 2015

Balkan Med J

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Background: Thyroid cancers are the most frequently occurring endocrine malignancy worldwide. In Turkey, thyroid cancers are ranked 2 nd on the incidence list in women, with a rate of 16.2%, but they are not included among the top 10 cancer types in men. Aims: To identify the contribution of the BRAF V600E mutation, and the RET/PTC1 and PAX8-PPARγ rearrangements in the diagnosis and differential diagnosis of follicular epithelial-derived thyroid lesions. Study Design: Retrospective clinical and molecular genetic study. Methods: A total of 86 thyroid cases diagnosed between 2001 and 2012 at the Department of Pathology were included in the retrospective study group. Samples best representing the lesion and comprising capsules were chosen in the selection of paraffin blocks pertaining to the cases. The BRAF V600E mutation, and the RET/PTC1 and PAX8-PPARγ rearrangements were investigated in all cases. Results: The BRAF V600E mutation was observed in 12 out of 37 papillary carcinoma cases (32.4%), in 1 out of 15 follicular carcinoma cases (6.6%), and in 1 out of 7 undifferentiated carcinoma cases (14.3%). No mutation was detected in benign lesions. The RET/PTC1 rearrangement was detected in 2 out of 7 undifferentiated carcinoma cases (28.6%), and in 1 out of 15 follicular carcinoma cases (6.6%). No gene rearrangement was detected in benign lesions. The PAX8-PPARγ rearrangement was detected in 5 out of 15 follicular thyroid carcinoma cases (33.3%) and in 1 out of 15 follicular adenoma cases (6.6%). Conclusion:The BRAF V600E mutation and RET/PTC1 rearrangement were effective in distinguishing the follicular epithelium-derived benign and malignant lesions of the thyroid in the resection materials. The BRAF V600E mutation was rather specific to papillary carcinoma in the thyroid, and in cases where the BRAF V600E mutation was detected, multi-centricity, lymph node metastasis and capsular invasion findings were observed more frequently compared to cases in which no mutation was observed. The PAX8-PPARγ rearrangement was observed to be more effective in the differentiation of adenomas and carcinomas in follicular neoplasms of the thyroid, whereas the RET/PTC1 analysis contributed to the differential diagnosis of papillary carcinoma histogenesis at a frequency of 29% in undifferentiated thyroid carcinomas.

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Section: Discussionsupporting

confidence: 67%

BRAFV600E Mutation, RET/PTC1 and PAX8-PPAR Gamma Rearrangements in Follicular Epithelium Derived Thyroid Lesions - Institutional Experience and Literature Review

Şahpaz¹,

Önal²,

Yeşilyurt³

et al. 2015

Balkan Med J

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“…Unlike BRAF and RAS mutations, RET/ PTC1 rearrangements are associated with a very low probability of dedifferentiation in papillary carcinomas [31,37,92]. The RET/PTC3 rearrangement, however, may predispose to dedifferentiation and more aggressive biologic behavior [93,94].…”

Section: Prognostic Molecular Markers In Thyroid Cancermentioning

confidence: 99%

Molecular Analysis of Thyroid Tumors

Bhaijee

Nikiforov

2011

Endocr Pathol

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Thyroid cancer is the most common endocrine malignancy, and its incidence is rising in the USA and other countries. Papillary and follicular thyroid carcinomas are the two most common types of thyroid cancer. Non-overlapping genetic alterations, including BRAF and RAS point mutations, and RET/PTC and PAX8/PPARγ rearrangements, are found in more than 70% of papillary and follicular thyroid carcinomas. These represent the most common genetic alterations in thyroid cancer, as well as molecular markers of diagnostic and prognostic significance. The use of these and other emerging molecular markers will likely improve the diagnosis of malignancy in thyroid nodules as well as facilitate more individualized operative and postoperative management. Herein, we provide a brief overview of the common genetic alterations in papillary and follicular thyroid carcinoma and discuss the diagnostic and prognostic significance thereof.

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“…Moreover, RET/PTC-positive PDTC are not associated with increased aggressiveness or poor patient survival and usually show histological evidence indicating coexistence with or possible evolution from a PTC often diagnosed as a classic, solid or tall cell variant PTC [7, 22, 57]. Concerning UTC, all previous studies reported an absence of RET/PTC rearrangements in this setting [22, 58]; only the study by Mochizuki et al [59], who studied seven composite UTC (UTC having a PTC component) and 14 single component UTC, has found the presence of a RET/PTC3 rearrangement in both components (UTC and PTC) of one composite UTC, whereas all 14 single component UTC were RET/PTC-negative. …”

Section: Ret/ptc and Pax8/pparγ Rearrangements In Pdtc And Utcmentioning

confidence: 99%

Genetic Alterations in Poorly Differentiated and Undifferentiated Thyroid Carcinomas

Soares¹,

Lima²,

Preto³

et al. 2011

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Thyroid gland presents a wide spectrum of tumours derived from follicular cells that range from well differentiated, papillary and follicular carcinoma (PTC and FTC, respectively), usually carrying a good prognosis, to the clinically aggressive, poorly differentiated (PDTC) and undifferentiated thyroid carcinoma (UTC).It is usually accepted that PDTC and UTC occur either de novo or progress from a pre-existing well differentiated carcinoma through a multistep process of genetic and epigenetic changes that lead to clonal expansion and neoplastic development. Mutations and epigenetic alterations in PDTC and UTC are far from being totally clarified. Assuming that PDTC and UTC may derive from well differentiated thyroid carcinomas (WDTC), it is expected that some PDTC and UTC would harbour genetic alterations that are typical of PTC and FTC. This is the case for some molecular markers (BRAF and NRAS) that are present in WDTC, PDTC and UTC. Other genes, namely P53, are almost exclusively detected in less differentiated and undifferentiated thyroid tumours, supporting a diagnosis of PDTC or, much more often, UTC. Thyroid-specific rearrangements RET/PTC and PAX8/PPARγ, on the other hand, are rarely found in PDTC and UTC, suggesting that these genetic alterations do not predispose cells to dedifferentiation. In the present review we have summarized the molecular changes associated with the two most aggressive types of thyroid cancer.

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RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components

Abstract: The high frequency of BRAF mutation and the absence of RET rearrangements in UC components from composite UCs supports the hypothesis that UCs may actually represent progressive malignant degeneration of a BRAF-mutated, well-differentiated thyroid carcinoma.

Cited by 36 publications

References 37 publications

BRAFV600E Mutation, RET/PTC1 and PAX8-PPAR Gamma Rearrangements in Follicular Epithelium Derived Thyroid Lesions - Institutional Experience and Literature Review

BRAFV600E Mutation, RET/PTC1 and PAX8-PPAR Gamma Rearrangements in Follicular Epithelium Derived Thyroid Lesions - Institutional Experience and Literature Review

Molecular Analysis of Thyroid Tumors

Genetic Alterations in Poorly Differentiated and Undifferentiated Thyroid Carcinomas

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