Chromosomal Rearrangements in Post‐Chernobyl Papillary Thyroid Carcinomas: Evaluation by Spectral Karyotyping and Automated Interphase FISH

Hieber, Ludwig; Huber, R.; Bauer, Verena; Schäffner, Quirin; Braselmann, Herbert; Thomas, Geraldine; Bogdanova, Tetiana; Zitzelsberger, Horst

doi:10.1155/2011/693691

Cited by 22 publications

(14 citation statements)

References 25 publications

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“…Interphase fluorescence in situ hybridization (FISH) is the gold standard method for detecting gene rearrangements in a single cell and is the most sensitive means for identifying and quantifying intratumoral genetic heterogeneity (Nakazawa et al 2009, Drieschner et al 2011, Hieber et al 2011. However, as FISH requires expert operators and is a time-consuming technology, it is rarely used, and no FISH-based studies on fine-needle aspiration (FNA) have been reported.…”

Section: Introductionmentioning

confidence: 99%

Assessing RET/PTC in thyroid nodule fine-needle aspirates: the FISH point of view

Caria¹,

Dettori²,

Frau³

et al. 2013

Endocrine-Related Cancer

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RET/PTC rearrangement and BRAF V600E mutation are the two prevalent molecular alterations associated with papillary thyroid carcinoma (PTC), and their identification is increasingly being used as an adjunct to cytology in diagnosing PTC. However, there are caveats associated with the use of the molecular approach in fine-needle aspiration (FNA), particularly for RET/PTC, that should be taken into consideration. It has been claimed that a clonal or sporadic presence of this abnormality in follicular cells can distinguish between malignant and benign nodules. Nevertheless, the most commonly used PCR-based techniques lack the capacity to quantify the number of abnormal cells. Because fluorescence in situ hybridization (FISH) is the most sensitive method for detecting gene rearrangement in a single cell, we compared results from FISH and conventional RT-PCR obtained in FNA of a large cohort of consecutive patients with suspicious nodules and investigated the feasibility of setting a FISH-FNA threshold capable of distinguishing non-clonal from clonal molecular events. For this purpose, a home brew break-apart probe, able to recognize the physical breakage of RET, was designed. While a R3% FISH signal for broken RET was sufficient to distinguish nodules with abnormal follicular cells, only samples with a R6.8% break-apart FISH signal also exhibited positive RT-PCR results. On histological analysis, all nodules meeting the R6.8% threshold proved to be malignant. These data corroborate the power of FISH when compared with RT-PCR in quantifying the presence of RET/PTC in FNA and validate the RT-PCR efficiency in detecting clonal RET/PTC alterations.

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Section: Introductionmentioning

confidence: 99%

Assessing RET/PTC in thyroid nodule fine-needle aspirates: the FISH point of view

Caria¹,

Dettori²,

Frau³

et al. 2013

Endocrine-Related Cancer

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“…Chromosomal abnormalities in both normal and atypical epithelial cells exfoliated in sputum were presented confirming that cellular genetic abnormalities of 3p22.1 and 10q22.3 reflect a field cancerization effect within the bronchial cells of individuals at high risk for developing cancer (43). Hieber et al screened cell cultures from papillary thyroid carcinomas for the presence of rearranged in transformation (RET)/papillary thyroid carcinomas (PTC) rearrangement (107). High frequency of RET rearrangement was found in Ukrainian patients after the Chernobil accident and the aberration was present only in a subset of tumor cells indicating genetic heterogeneity.…”

Section: Wide Range Of Applicationsmentioning

confidence: 95%

State‐of‐the‐art FISHing: Automated analysis of cytogenetic aberrations in interphase nuclei

et al. 2012

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Interphase fluorescence in situ hybridization (i‐FISH) is a powerful tool for visualizing various molecular targets in non‐dividing cells. Manual scoring of i‐FISH signals is a labor intensive, time‐consuming, and error‐prone process liable to subjective interpretation. Automated evaluation of signal patterns provides the opportunity to overcome these difficulties. The first report on automated i‐FISH analysis has been published 20 years ago and since then several applications have been introduced in the fields of oncology, and prenatal and fertility screening. In this article, we provide an insight into the automated i‐FISH analysis including its course, brief history, clinical applications, and advantages and challenges. The lack of guidelines for describing new automated i‐FISH methods hampers the precise comparison of performance of various applications published, thus, we make a proposal for a panel of parameters essential to introduce and standardize new applications and reproduce previously described technologies. © 2012 International Society for Advancement of Cytometry

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“…However, this method provides important information on the percentage of cells harboring the RET rearrangement and on its clonal/non-clonal occurrence (21,22). More recently, automated interphase FISH was successfully applied to detect RET/PTC in PTC primary cultures, a method that, suitably modified for clinical practice, could allow the analysis of a larger number of cells per sample and overcome a possible bias of the operator (38).…”

Section: Methods Of Detection For Ret/ptc Rearrangementsmentioning

confidence: 99%

RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint

Marotta¹,

Guerra²,

Sapio³

et al. 2011

European Journal of Endocrinology

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Cytological examination of fine needle aspiration biopsy is the primary means for distinguishing benign from malignant nodules. However, as inconclusive cytology is very frequent, the introduction of molecular markers in the preoperative diagnosis of thyroid nodules has been proposed in recent years. In this article, we review the clinical implications of preoperative detection of rearrangements of the RET gene (RET/papillary thyroid carcinoma (PTC)) in thyroid nodules. The prevalence of RET/PTC in PTC depends on the histological subtypes, geographical factors, radiation exposure, and detection method. Initially, RET/PTC was considered an exclusive PTC hallmark and later it was also found sporadically in benign thyroid lesions. More recently, the very sensitive detection methods, interphase fluorescence in situ hybridization (FISH) and Southern blot on RT-PCR amplicons, demonstrated that the oligoclonal occurrence of RET rearrangement in benign thyroid lesions is not a rare event and suggested that it could be associated with a faster enlargement in benign nodules. For this reason, RET/PTC cannot be considered as an absolute marker of PTC, and its diagnostic application must be limited to assays able to distinguish between clonal and oligoclonal expression. Detection of RET/PTC by quantitative assays will be useful for diagnostic purposes in cytology specimens when a precise cutoff will be fixed in a clinical setting. Until that time, less sensitive RET/PTC detection methods and FISH analysis remain the most appropriate means to refine inconclusive cytology. Future studies with a long follow-up will further clarify the clinical significance of low level of RET rearrangements in benign nodules.

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Chromosomal Rearrangements in Post‐Chernobyl Papillary Thyroid Carcinomas: Evaluation by Spectral Karyotyping and Automated Interphase FISH

Cited by 22 publications

References 25 publications

Assessing RET/PTC in thyroid nodule fine-needle aspirates: the FISH point of view

Assessing RET/PTC in thyroid nodule fine-needle aspirates: the FISH point of view

State‐of‐the‐art FISHing: Automated analysis of cytogenetic aberrations in interphase nuclei

RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint

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