Molecular differential diagnosis of follicular thyroid carcinoma and adenoma based on gene expression profiling by using formalin-fixed paraffin-embedded tissues

Pfeifer, Aleksandra; Wojtaś, Bartosz; Oczko-Wojciechowska, Małgorzata; Kukulska, Aleksandra; Czarniecka, Agnieszka; Eszlinger, Markus; Musholt, Thomas J.; Stokowy, Tomasz; Świerniak, Michał; Stobiecka, Ewa; Rusinek, Dagmara; Tyszkiewicz, Tomasz; Kowal, Monika; Jarząb, Michał; Hauptmann, Steffen; Lange, Dariusz; Paschke, Ralf; Jarząb, Barbara

doi:10.1186/1755-8794-6-38

Cited by 30 publications

(31 citation statements)

References 39 publications

(52 reference statements)

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“…Therefore, we propose that an accuracy of approximately 80% constitutes a plausible limit of FTC vs. FTA gene classifier performance when analysis is performed in postoperative formalin-fixed material [27]. …”

Section: Discussionmentioning

confidence: 99%

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours

Wojtaś

Pfeifer

Oczko-Wojciechowska

et al. 2017

IJMS

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Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent set of 71 follicular neoplasms from formaldehyde-fixed paraffin embedded (FFPE) tissue material. We confirmed differential expression for 7 genes (CPQ, PLVAP, TFF3, ACVRL1, ZFYVE21, FAM189A2, and CLEC3B). Finally, we created a classifier that distinguished between FTC and FTA with an accuracy of 78%, sensitivity of 76%, and specificity of 80%, based on the expression of 4 genes (CPQ, PLVAP, TFF3, ACVRL1). In our study, we have demonstrated that meta-analysis is a valuable method for selecting possible molecular markers. Based on our results, we conclude that there might exist a plausible limit of gene classifier accuracy of approximately 80%, when follicular tumors are discriminated based on formalin-fixed postoperative material.

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Section: Discussionmentioning

confidence: 99%

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours

Wojtaś

Pfeifer

Oczko-Wojciechowska

et al. 2017

IJMS

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“…The pre-operative diagnosis of FTC is very problematic because of its similarity to FAs, and the distinction between both lesions is currently based mainly on the presence of capsular or vascular invasion. FTC and FA are not only similar with respect to histopathological features but also show a common genetic background [71]. RAS somatic mutations and PAX8/PPARγ rearrangements, the key FTC alterations, were detected in both FTCs and FAs [72].…”

Section: Follicular Thyroid Carcinomamentioning

confidence: 99%

Heterogeneity of Thyroid Cancer

et al. 2018

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There are 5 main histological types of thyroid cancers (TCs): papillary, follicular (also known as differentiated), poorly differentiated, anaplastic (the most aggressive form), and medullary TC, and only the latter arises from thyroid C cells. These different forms of TCs show significant variability, both among and within tumours. This great variation is particularly notable among the first 4 types, which all originate from thyroid follicular cells. Importantly, this heterogeneity is not limited to histopathological diversity only but is also manifested as variation in several genetic and/or epigenetic alterations, the numbers of interactions between the tumour and surrounding microenvironment, and interpatient differences, for example. All these factors contribute to the great complexity in the development of a tumour from cancer cells. In the present review, we summarise the knowledge accumulated about the heterogeneity of TCs. Further research in this direction should help to gain a better understanding of the underlying mechanisms contributing to the development and diversity of TCs, paving the way toward more effective treatment strategies.

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“…Also the employment of 5-gene classifier as demonstrated in study by Pfeifer at al. was successfully applied as a marker for FTC and FA in formalin-fixed paraffin-embedded samples [47]. Although the functional or biological rationale of the markers used in those studies remains not entirely understood for thyroid gland, they proved to be of a great accuracy.…”

Section: Discussionmentioning

confidence: 99%

Expression of ARE-binding proteins AUF1 and HuR in follicular adenoma and carcinoma of thyroid gland

Trojanowicz¹,

Sekulla²,

Dralle³

et al. 2016

neo

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Both adenylate-uridylate rich elements binding proteins AUF1 and HuR may participate in thyroid carcinoma progression. In this study we investigated the expression of both factors on a protein level with a special focus on follicular adenoma and follicular thyroid carcinoma. By employment of immunofluorescence and western blot on 68 thyroid tissues including 7 goiter, 16 follicular adenoma (4 adenomatous hyperplasia), 19 follicular thyroid carcinomas, 13 papillary thyroid carcinomas and 14 undifferentiated thyroid carcinomas we investigated protein expression of AUF1 and HuR. In addition to previous results we demonstrated that AUF1 and HuR are significantly up-regulated in carcinoma tissues as compared with follicular adenoma or goiter tissues. Furthermore, by evaluation of AUF1 or HuR expression, or combination of both proteins on total tissue lysates, we were able to demonstrate a significant difference between follicular adenoma and follicular thyroid carcinoma.Overexpression of AUF1 and HuR is a common finding observed in thyroid malignancy. Analysis of the tissues obtained by surgical resection as demonstrated in this study is comparable to a fine needle aspiration and in combination with AUF1/ HuR immuno-analysis may support the conventional immunohistological investigations. The promising results of this study were performed on relatively small collective, but justify future development of a quick thyroid diagnostic test on larger cohort of the patients, especially for thyroid samples which are inadequate for histological examinations.

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Molecular differential diagnosis of follicular thyroid carcinoma and adenoma based on gene expression profiling by using formalin-fixed paraffin-embedded tissues

Cited by 30 publications

References 39 publications

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours

Heterogeneity of Thyroid Cancer

Expression of ARE-binding proteins AUF1 and HuR in follicular adenoma and carcinoma of thyroid gland

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