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This version published online on February 15, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-2028
A more recent version of this article appeared on May 1, 2005
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*Thyroid Cancer

Submitted on October 13, 2004
Accepted on February 3, 2005

Genetic classification of benign and malignant thyroid follicular neoplasia based on a 3-gene combination

Frank Weber, Lei Shen, Micheala A. Aldred, Carl D. Morrison, Andrea Frilling, Motoyasu Saji, Frank Schuppert, Christoph E. Broelsch, Matthew D. Ringel, and Charis Eng*

Clinical Cancer Genetics Program (FW, CE), Human Cancer Genetics Program (FW, MDR, CE), Comprehensive Cancer Center (MS, MDR, CE), Division of Endocrinology and Metabolism (MS, MDR) and Division of Human Genetics (CE), Department of Internal Medicine, Department of Molecular Virology, Immunology and Medical Genetics (FW, CE), Division of Epidemiology and Biometrics (LS), Department of Pathology (CDM), The Ohio State University, Columbus, OH, USA; Department of General Surgery and Transplantation, University of Essen, Essen, Germany (FW, AF, CEB), Department of Internal Medicine, Hospital Bad Oeynhausen, Bad Oeynhausen, Germany (FS); Division of Medical Genetics, University of Leicester, Leicester, UK (MAA); Cancer Research UK Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK (CE)

* To whom correspondence should be addressed. E-mail: eng.25{at}osu.edu.

Thyroid carcinoma is a common endocrine cancer with a favorable prognosis if subjected to timely treatment. However, the clinical identification of follicular thyroid carcinoma (FTC) among patients with benign thyroid nodules is still a challenge. Preoperative fine needle aspiration-based cytology cannot always differentiate follicular carcinomas from benign follicular neoplasias. Because current methods fail to improve preoperative diagnosis of thyroid nodules, new molecular-based diagnoses should be explored. We conducted a microarray-based study to reveal the genetic profiles unique to FTC and FA, to identify the most parsimonious number of genes that could accurately differentiate between benign and malignant follicular thyroid neoplasia. We confirmed our data by quantitative RT-PCR and immunohistochemistry in two independent validation sets with a total of 114 samples. We were able to identify 3 genes, Cyclin D2, PCSK2 and PLAB, that allow the accurate molecular classification of FTC and FA. Two independent validation sets revealed that the combination of these 3 genes could differentiate FTC from FA with a sensitivity of 100%, specificity of 94.7% and accuracy of 96.7%. In addition our model allowed the identification of FV-PTC with an accuracy of 85.7%. Three-gene profiling of thyroid nodules can accurately predict the diagnosis of FTC and FA with high sensitivity and specificity, thus identifying promising targets for further investigation to ultimately improve preoperative diagnosis.
Key words: Follicular Thyroid Carcinoma • Diagnostic • Microarray • Follicular Thyroid Adenoma • Thyroid Nodule




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