PPARγ Staining as a Surrogate for PAX8/PPARγ Fusion Oncogene Expression in Follicular Neoplasms: Clinicopathological Correlation and Histopathological Diagnostic Value

Şahi̇n, Mustafa; Allard, Brandon L.; Yates, Martin T.; Powell, J. Gregory; Wang, Xiao Li; Hay, Ian; Zhao, Ying; Goellner, John R.; Sebo, Thomas J.; Grebe, Stefan K.; Eberhardt, Norman L.; McIver, Bryan

doi:10.1210/jc.2004-1203

Cited by 73 publications

(55 citation statements)

References 25 publications

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“…While the Ras mutation is not restricted to a particular histological type, PAX8/PPARg rearrangement mainly presents with follicular neoplasms and a small portion of follicular variants of papillary thyroid cancers (Dwight et al 2003, Nikiforova et al 2003, Kroll 2004, Lacroix et al 2004, Koenig 2010, Nikiforov & Nikiforova 2011. Because the expression of PPFP indicates a favorable clinical presentation and prognosis, FTCs presenting with PAX8/PPARg rearrangement are thought to be a less aggressive subtype (Sahin et al 2005). Although it is expressed at a lower frequency in follicular thyroid adenoma, PPFP is believed to play an important role in thyroid tumorigenesis, probably at an early stage (Nikiforova et al 2002, Gregory Powell et al 2004, Reddi et al 2007.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

Li¹,

Wang²,

Liu³

et al. 2012

Endocrine-Related Cancer

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The fusion gene encoding the thyroid-specific transcription factor PAX8 and peroxisome proliferator-activated receptor g (PPARg (PPARG)) (designated as the PPFP gene) is oncogenic and implicated in the development of follicular thyroid carcinoma (FTC). The effects of PPFP transfection on the biological characteristics of Nthy-ori 3-1 cells were studied by MTT assay, colony formation, soft-agar colony formation, and scratch wound-healing assays as well as by flow cytometry. Furthermore, the differentially expressed proteins were analyzed on 2-DE maps and identified by MALDI-TOF-MS. Validation of five identified proteins (prohibitin, galectin-1, cytokeratin 8 (CK8), CK19, and HSP27) was determined by western blot analysis. PPFP not only significantly increased the viability, proliferation, and mobility of the Nthy-ori 3-1 cells but also markedly inhibited cellular apoptosis. Twenty-eight differentially expressed proteins were identified, among which 19 proteins were upregulated and nine proteins were downregulated in Nthy-ori 3-1 PPFP (Nthy-ori 3-1 cells transfected with PPFP). The western blot results, which were consistent with the proteome analysis results, showed that prohibitin was downregulated, whereas galectin-1, CK8, CK19, and HSP27 were upregulated in Nthy-ori 3-1 PPFP . Our results suggest that PPFP plays an important role in malignant thyroid transformation. Proteomic analysis of the differentially expressed proteins in PPFP-transfected cells provides important information for further study of the carcinogenic mechanism of PPFP in FTCs.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

Li¹,

Wang²,

Liu³

et al. 2012

Endocrine-Related Cancer

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“…At lease 10 types of RET/PTC rearrangement have been identified, which differ by their 5k partner genes, with RET/PTC1, RET/PTC2, and RET/PTC3 being the most common and occurring mainly in PTC and some benign adenomas. The PAX8-PPARg occurs both in FTC and benign thyroid adenoma (Cheung et al 2003, Sahin et al 2005. The recently discovered activating mutation in BRAF (the gene for the B-type Raf kinase, BRAF), the focus of this review, represents the most common genetic alteration in thyroid cancer.…”

Section: Introductionmentioning

confidence: 99%

BRAF mutation in thyroid cancer

Xing¹

2005

Endocrine Related Cancer

1,186

976

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Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding in thyroid cancer is the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf kinase, BRAF). Since the initial report of this mutation in thyroid cancer 2 years ago, rapid advancements have been made. BRAF mutation is the most common genetic alteration in thyroid cancer, occurring in about 45% of sporadic papillary thyroid cancers (PTCs), particularly in the relatively aggressive subtypes, such as the tall-cell PTC. This mutation is mutually exclusive with other common genetic alterations, supporting its independent oncogenic role, as demonstrated by transgenic mouse studies that showed BRAF mutation-initiated development of PTC and its transition to anaplastic thyroid cancer. BRAF mutation is mutually exclusive with RET/PTC rearrangement, and also displays a reciprocal age association with this common genetic alteration in thyroid cancer. The T1799A BRAF mutation occurs exclusively in PTC and PTC-derived anaplastic thyroid cancer and is a specific diagnostic marker for this cancer when identified in cytological and histological specimens. This mutation is associated with a poorer clinicopathological outcome and is a novel independent molecular prognostic marker in the risk evaluation of thyroid cancer. Moreover, preclinical and clinical evaluations of the therapeutic value of novel specific mitogen-activated protein kinase pathway inhibitors in thyroid cancer are anticipated. This newly discovered BRAF mutation may prove to have an important impact on thyroid cancer in the clinic.Endocrine-Related Cancer (2005) 12 245-262

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“…It was reported in the literature that papillary thyroid carcinoma cases found to have a BRAF V600E mutation were more aggressive in studies assessing the relation between BRAF V600E mutation and prognosis and that metastasis outside the thyroid, lymph node and distant metastases increased, that there was a relation between advanced age and advanced stage tumor and that there was resistance to radioactive iodine therapy (18,43). In line with the literature and Turkish data, a BRAF V600E mutation was detected in 12 out of 37 papillary thyroid carcinoma cases (32.4%).…”

Section: Discussionmentioning

confidence: 99%

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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PPARγ Staining as a Surrogate for PAX8/PPARγ Fusion Oncogene Expression in Follicular Neoplasms: Clinicopathological Correlation and Histopathological Diagnostic Value

Cited by 73 publications

References 25 publications

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

BRAF mutation in thyroid cancer

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

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