Open Access Research article

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

Aleksandra Pfeifer15, Bartosz Wojtas1, Malgorzata Oczko-Wojciechowska1, Aleksandra Kukulska1, Agnieszka Czarniecka2, Markus Eszlinger6, Thomas Musholt7, Tomasz Stokowy15, Michal Swierniak18, Ewa Stobiecka4, Dagmara Rusinek1, Tomasz Tyszkiewicz1, Monika Kowal1, Michal Jarzab3, Steffen Hauptmann9, Dariusz Lange4, Ralf Paschke6 and Barbara Jarzab1*

Author Affiliations

1 Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, Gliwice 44-101, Poland

2 Clinic of Oncological and Reconstructive Surgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, Gliwice 44-101, Poland

3 Radiotherapy and Chemotherapy Clinic, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, Gliwice 44-101, Poland

4 Tumor Pathology Department, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, Gliwice 44-101, Poland

5 Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, Gliwice Poland

6 Division of Endocrinology and Nephrology, University of Leipzig Leipzig, Germany

7 Department of General, Visceral, and Transplantation Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Germany

8 Genomic Medicine, Department of General, Transplant, and Liver Surgery, Medical University of Warsaw Warsaw, Poland

9 Department of Pathology, Martin Luther University Halle-Wittenberg Halle (Saale), Germany

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BMC Medical Genomics 2013, 6:38  doi:10.1186/1755-8794-6-38

Published: 7 October 2013

Abstract

Background

Differential diagnosis between malignant follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort. Molecular markers may potentially support a differential diagnosis between FTC and FTA in postoperative specimens. The purpose of this study was to derive molecular support for differential post-operative diagnosis, in the form of a simple multigene mRNA-based classifier that would differentiate between FTC and FTA tissue samples.

Methods

A molecular classifier was created based on a combined analysis of two microarray datasets (using 66 thyroid samples). The performance of the classifier was assessed using an independent dataset comprising 71 formalin-fixed paraffin-embedded (FFPE) samples (31 FTC and 40 FTA), which were analysed by quantitative real-time PCR (qPCR). In addition, three other microarray datasets (62 samples) were used to confirm the utility of the classifier.

Results

Five of 8 genes selected from training datasets (ELMO1, EMCN, ITIH5, KCNAB1, SLCO2A1) were amplified by qPCR in FFPE material from an independent sample set. Three other genes did not amplify in FFPE material, probably due to low abundance. All 5 analysed genes were downregulated in FTC compared to FTA. The sensitivity and specificity of the 5-gene classifier tested on the FFPE dataset were 71% and 72%, respectively.

Conclusions

The proposed approach could support histopathological examination: 5-gene classifier may aid in molecular discrimination between FTC and FTA in FFPE material.

Keywords:
Follicular thyroid adenoma; Follicular thyroid cancer; Gene expression; Microarray; Formalin-fixed paraffin-embedded blocks