Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P= 0.01) and poorer clinical outcome (P= 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions.

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Abstract 2770: Spatio-temporal genetic heterogeneity and clonal evolution in advanced papillary thyroid carcinomas and matched distant metastases

10.1158/1538-7445.sabcs18-2770 ◽

2019 ◽

Author(s):

Sara Gil-Bernabe ◽

Noa Feas Rodríguez ◽

Miriam Vega Herrero ◽

Jose Javier Estébanez García ◽

Ginesa M. Garcia-Rostan

Keyword(s):

Genetic Heterogeneity ◽

Clonal Evolution ◽

Distant Metastases ◽

Papillary Thyroid ◽

Thyroid Carcinomas ◽

Spatio Temporal

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Deep sequencing of KIT, MET, PIK3CA, and PTEN hotspots in papillary thyroid carcinomas with distant metastases

Endocrine Related Cancer ◽

10.1530/erc-14-0361 ◽

2014 ◽

Vol 21 (5) ◽

pp. L23-L26 ◽

Cited By ~ 8

Author(s):

G. Gandolfi ◽

D. de Biase ◽

V. Sancisi ◽

M. Ragazzi ◽

G. Acquaviva ◽

...

Keyword(s):

Deep Sequencing ◽

Distant Metastases ◽

Papillary Thyroid ◽

Thyroid Carcinomas

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Conventional Ultrasonography and Real Time Ultrasound Elastography in the Differential Diagnosis of Degenerating Cystic Thyroid Nodules Mimicking Malignancy and Papillary Thyroid Carcinomas

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2013.14.2.935 ◽

2013 ◽

Vol 14 (2) ◽

pp. 935-940 ◽

Cited By ~ 4

Author(s):

Hong-Xun Wu ◽

Bing-Jie Zhang ◽

Jun Wang ◽

Bei-Lin Zhu ◽

Ya-Ping Zang ◽

...

Keyword(s):

Differential Diagnosis ◽

Real Time ◽

Thyroid Nodules ◽

Ultrasound Elastography ◽

Papillary Thyroid ◽

Thyroid Carcinomas

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Solitary Liver Metastasis from Follicular Variant Papillary Thyroid Carcinoma: A Case Report

Bangladesh Journal of Nuclear Medicine ◽

10.3329/bjnm.v22i2.51768 ◽

2021 ◽

Vol 22 (2) ◽

pp. 146-149

Author(s):

Rahima Perveen ◽

Jasmin Ferdous ◽

Sharmin Quddus ◽

Tapati Mandal

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Distant Metastases ◽

Differentiated Thyroid Carcinoma ◽

Papillary Thyroid ◽

Follicular Variant ◽

Thyroid Carcinomas ◽

Visceral Metastases ◽

Solitary Liver

Papillary and follicular thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Distant metastases are rare events at the onset of DTC. Sites of metastases from follicular thyroid cancer (FTC) are usually osseous, and those from papillary thyroid cancer (PTC) metastasize to regional nodal basins and the lungs. Visceral metastases are rare, but the involvement of multiple sites has been reported so far. Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare.We present the case of a patient with follicular variant of papillary thyroid carcinoma (FVPTC) unusually involving the liver. Bangladesh J. Nuclear Med. 22(2): 146-149, Jul 2019

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Immunohistochemical Expression of HBME-1, E-cadherin, and CD56 in the Differential Diagnosis of Thyroid Nodules

Medicina ◽

10.3390/medicina48100074 ◽

2012 ◽

Vol 48 (10) ◽

pp. 74 ◽

Cited By ~ 1

Author(s):

Arturs Ozolins ◽

Zenons Narbuts ◽

Ilze Strumfa ◽

Guna Volanska ◽

Kaspars Stepanovs ◽

...

Keyword(s):

Differential Diagnosis ◽

Follicular Carcinoma ◽

Needle Aspiration ◽

Thyroid Tumors ◽

Papillary Thyroid ◽

Thyroid Carcinomas ◽

Diagnostic Potential ◽

Ancillary Test ◽

Benign Thyroid ◽

E Cadherin

Background and Objective. Distinction between benign and malignant thyroid tumors is essential for proper clinical management. The aim of this study was to evaluate the diagnostic potential of a set of 3 molecular markers in the differential diagnosis of thyroid tumors. Material and Methods. Immunohistochemistry for HBME-1, E-cadherin (E-CAD), and CD56 was carried out in 36 follicular adenomas, 77 colloid goiters, 36 papillary thyroid carcinomas, and 14 follicular carcinomas. Sixty-eight thyroid fine needle aspiration (FNA) cases confirmed by subsequent surgical resection specimens were selected. Immunocytochemistry for HBME-1, E-CAD, and CD56 was performed in these cases, including 25 papillary thyroid carcinomas, 1 follicular carcinoma, 22 follicular adenomas, and 20 colloid goiters. Results. PTC was characterized by a decreased expression of E-CAD and CD56 contrary to the surrounding benign thyroid tissues. There was no HBME-1 expression in benign thyroid tissues, but it was high in papillary thyroid carcinomas and weak in follicular adenomas. The expression of E-CAD and CD56 was significantly higher in follicular adenomas than in the surrounding thyroid tissues. Analyzing the FNA material, HBME-1 expression was documented in 96% of papillary thyroid carcinomas, but there was no expression in the benign lesions. E-CAD and CD56 expression was significantly weakened in papillary thyroid carcinomas, but enhanced in follicular adenomas. Conclusions. HBME-1 was found only in malignant lesions and can be considered the most sensitive, specific single marker in papillary thyroid carcinomas. CD56 and E-CAD can assist in the decision-making on the benign and malignant nature of the nodule. Immunocytochemistry is of value as an ancillary test to enhance the diagnostic accuracy of thyroid FNA samples.

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BRAFV600E mutation and expression of proangiogenic molecular markers in papillary thyroid carcinomas

Acta Endocrinologica ◽

10.1530/eje-11-0283 ◽

2011 ◽

Vol 165 (3) ◽

pp. 455-463 ◽

Cited By ~ 18

Author(s):

Cosimo Durante ◽

Giovanni Tallini ◽

Efisio Puxeddu ◽

Marialuisa Sponziello ◽

Sonia Moretti ◽

...

Keyword(s):

Gene Expression ◽

Growth Factors ◽

Kinase Inhibitors ◽

Thyroid Cell ◽

Mrna Levels ◽

Papillary Thyroid ◽

Thyroid Carcinomas ◽

Neuropilin 1 ◽

The Impact

ObjectiveTyrosine kinase inhibitors (TKIs) are evaluated for treatment of radioiodine refractory thyroid cancer. Their effects in this setting are based on blockade of proangiogenic signaling mediated by receptors for vascular endothelial growth factors (VEGFs) and platelet-derived growth factors (PDGF). Most TKIs also block other cancer-relevant kinases, such as B-type Raf kinase (BRAF), which are constitutively activated in approximately half of papillary thyroid carcinomas (PTCs), but the impact of these effects is not clear.DesignThe aim of our study was to investigate the impact of BRAFV600E on proangiogenic gene expression and microvascular features of PTCs.MethodsmRNA levels for VEGFA, VEGF receptors, and coreceptors (VEGFRs 1, 2, and 3, neuropilin-1), and PDGF receptor β (PDGFRβ or PDGFRB) were measured with real-time PCR in BRAFV600E (n=55) and wild-type BRAF (BRAF-wt; n=35) PTCs. VEGF and VEGFR protein expression and microvessel densities (MVD) and lymphatic vessel densities (LVDs) were assessed by immunohistochemistry in 22 of the 90 PTCs (including 11 BRAFV600E cases). Angiogenic gene expression was also studied in vitro after induction/silencing of the BRAFV600E mutation in thyrocyte lines.ResultsTranscript levels of proangiogenic factors were significantly lower in BRAFV600E PTCs versus BRAF-wt PTCs (P<0.0001), but MVD and LVDs were not significantly different. VEGFA mRNA levels in thyroid cell lines decreased when BRAFV600E mutation was induced (P=0.01) and increased when it was silenced (P=0.01).ConclusionsCompared with BRAF-wt PTCs, those harboring BRAFV600E exhibit downregulated VEGFA, VEGFR, and PDGFRβ expression, suggesting that the presence of BRAF mutation does not imply a stronger prediction of response to drugs targeting VEGF and PDGFB signaling pathways.

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