Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings

Sapio, Maria Rosaria; Posca, Daniela; Raggioli, Angelo; Guerra, Anna; Marotta, Vincenzo; Deandrea, Maurilio; Motta, Manuela; Limone, Paolo Piero; Troncone, Giancarlo; Caleo, Alessia; Rossi, Guido; Fenzi, Gianfranco; Vitale, Mario

doi:10.1111/j.1365-2265.2007.02800.x

Cited by 148 publications

(94 citation statements)

References 19 publications

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“…Recent studies reported that the BRAF mutation is a highly accurate marker of malignancy for thyroid nodules sampled by FNAB [205][206][207][208][209]. However, the most frequent diagnostic problems in FNAB samples are indeterminate follicular tumors and suspicion of malignancy according to the Bethesda system.…”

Section: Molecular Targets In Histopathological Diagnosis and Classifmentioning

confidence: 99%

An update on molecular biology of thyroid cancers

Ömür

Baran

2014

Critical Reviews in Oncology/Hematology

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Section: Molecular Targets In Histopathological Diagnosis and Classifmentioning

confidence: 99%

An update on molecular biology of thyroid cancers

Ömür

Baran

2014

Critical Reviews in Oncology/Hematology

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“…A number of groups have suggested molecular markers to assist in the diagnosis of papillary thyroid carcinoma from fine-needle aspiration specimens. 40,41 Sapio et al 42 recently proposed detection of ret/PTC, TRK and BRAF (V600E) in fine-needle aspiration specimens as a diagnostic adjunctive tool in the evaluation of thyroid nodules. They found that the discovery of oncogenes in fineneedle aspiration specimens suspicious for malignancy guided the extent of surgical resection, changing the surgery from diagnostic to therapeutic in five cases.…”

Section: Applicationsmentioning

confidence: 99%

A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples

et al. 2007

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Follicular variant of papillary thyroid carcinoma is a lesion that frequently causes difficulties from a diagnostic perspective in the laboratory. The purpose of this study was to interrogate a cohort of archival thyroid lesions using gene expression analysis of a panel of markers proposed to have utility as adjunctive markers in the diagnosis of thyroid neoplasia and follicular variant of papillary thyroid carcinoma in particular. Laser Capture Microdissection was used to procure pure cell populations for extraction. In addition a novel, multiplex preamplification technique was used to facilitate analysis of multiple targets. The panel comprised: HLA-DMA, HLA-DBQ1, CD74, CSNK1G2, IRF3, KRAS2, LYN, MT1K, MT1X, RAB23, TGFB1 and TOP2A, with CDKN1B as an endogenous control. Expression profiles for each target were generated using TaqMan s Real-Time PCR. HLA-DMA, HLA-DQB1, MT1X, CSNK1G2 and RAB23 were found to be differentially expressed (Po0.05) when comparing follicular adenoma and follicular variant of papillary thyroid carcinoma. Comparison of follicular adenoma and follicular thyroid carcinoma groups showed significant differential expression for MT1K, MT1X and RAB23 (Po0.05). Comparison of the papillary thyroid carcinoma group (classic and follicular variants) and the follicular adenoma group showed differential expression for CSNK1G2, HLA-DQB1, MT1X and RAB23 (Po0.05). Finally, KRAS2 was found to be differentially expressed (Po0.05) when comparing the papillary thyroid carcinoma and follicular thyroid carcinoma groups. This panel of molecular targets discriminates between follicular adenoma, papillary thyroid carcinoma, follicular variant of papillary thyroid carcinoma and follicular thyroid carcinoma by their expression repertoires. It may have utility for broader use in the setting of fine-needle aspiration cytology and could improve the definitive diagnosis of certain categories of thyroid malignancy.

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“…We used the forward primer for H4 gene and the reverse primer for the tyrosine kinase domain of RET (Supplementary Table S1). PCR conditions were performed according to a previously described protocol (Sapio et al 2007). Afterwards, 10 ml of the PCR product were analyzed by electrophoresis in a 1.5% agarose gel.…”

Section: Human Ptc Samplesmentioning

confidence: 99%

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Romitti¹,

Wajner²,

Ceolin³

et al. 2016

Endocrine-Related Cancer

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Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metast atic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in human PTC cell lines (K1 and TPC-1 cells) or tumor samples. DIO3 mRNA and activity were evaluated by real-time PCR and ion-exchange column chromatography respectively. Western blot analysis was used to determine the levels of D3 protein. DIO3 gene silencing was performed via siRNA transfection. DIO3 mRNA levels and activity were readily detected in K1 (BRAF V600E ) and, at lower levels, in TPC-1 (RET/PTC1) cells (P!0.007 and PZ0.02 respectively). Similarly, DIO3 mRNA levels were higher in PTC samples harboring the BRAF V600E mutation as compared with those with RET/PTC1 rearrangement or negative for these mutations (P!0.001). Specific inhibition of BRAF oncogene (PLX4032, 3 mM), MEK (U0126, 10-20 mM) or p38 (SB203580, 10-20 mM) signaling was associated with decreases in DIO3 expression in K1 and TPC-1 cells. Additionally, the blockage of the sonic hedgehog (SHH) pathway by cyclopamine (10 mM) resulted in markedly decreases in DIO3 mRNA levels. Interestingly, siRNA-mediated DIO3 silencing induced decreases on cyclin D1 expression and partial G1 phase cell cycle arrest, thereby downregulating cell proliferation. In conclusion, sustained activation of the MAPK and SHH pathways modulate the levels of DIO3 expression in PTC. Importantly, DIO3 silencing was associated with decreases in cell proliferation, thus suggesting a D3 role in tumor growth and aggressiveness.

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Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings

Cited by 148 publications

References 19 publications

An update on molecular biology of thyroid cancers

An update on molecular biology of thyroid cancers

A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

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