Three-gene molecular diagnostic model for thyroid cancer

Nijaguna B. Prasad, Jeanne Kowalski, Hua Ling Tsai, Kristin Talbot, Helina Somervell, Guennadi Kouniavsky, Yongchun Wang, Alan P B Dackiw, William H. Westra, Douglas P. Clark, Steven K. Libutti, Christopher B. Umbricht, Martha A. Zeiger

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28 Citations (Scopus)

Abstract

Background: The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated "suspicious or indeterminate", but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology. Methods: Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology. Results: Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of≥0.95 (80% sensitivity; 100% specificity) and≥0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively. Conclusions: Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules.

Original languageEnglish (US)
Pages (from-to)275-284
Number of pages10
JournalThyroid
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2012

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Molecular Models
Molecular Pathology
Fine Needle Biopsy
Thyroid Neoplasms
Cell Biology
Thyroid Nodule
Thyroid Gland
Genes
Immunohistochemistry
Real-Time Polymerase Chain Reaction
Neoplasms
Microarray Analysis
ROC Curve
Area Under Curve

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Prasad, N. B., Kowalski, J., Tsai, H. L., Talbot, K., Somervell, H., Kouniavsky, G., ... Zeiger, M. A. (2012). Three-gene molecular diagnostic model for thyroid cancer. Thyroid, 22(3), 275-284. https://doi.org/10.1089/thy.2011.0169

Three-gene molecular diagnostic model for thyroid cancer. / Prasad, Nijaguna B.; Kowalski, Jeanne; Tsai, Hua Ling; Talbot, Kristin; Somervell, Helina; Kouniavsky, Guennadi; Wang, Yongchun; Dackiw, Alan P B; Westra, William H.; Clark, Douglas P.; Libutti, Steven K.; Umbricht, Christopher B.; Zeiger, Martha A.

In: Thyroid, Vol. 22, No. 3, 01.03.2012, p. 275-284.

Research output: Contribution to journalArticle

Prasad, NB, Kowalski, J, Tsai, HL, Talbot, K, Somervell, H, Kouniavsky, G, Wang, Y, Dackiw, APB, Westra, WH, Clark, DP, Libutti, SK, Umbricht, CB & Zeiger, MA 2012, 'Three-gene molecular diagnostic model for thyroid cancer', Thyroid, vol. 22, no. 3, pp. 275-284. https://doi.org/10.1089/thy.2011.0169
Prasad NB, Kowalski J, Tsai HL, Talbot K, Somervell H, Kouniavsky G et al. Three-gene molecular diagnostic model for thyroid cancer. Thyroid. 2012 Mar 1;22(3):275-284. https://doi.org/10.1089/thy.2011.0169
Prasad, Nijaguna B. ; Kowalski, Jeanne ; Tsai, Hua Ling ; Talbot, Kristin ; Somervell, Helina ; Kouniavsky, Guennadi ; Wang, Yongchun ; Dackiw, Alan P B ; Westra, William H. ; Clark, Douglas P. ; Libutti, Steven K. ; Umbricht, Christopher B. ; Zeiger, Martha A. / Three-gene molecular diagnostic model for thyroid cancer. In: Thyroid. 2012 ; Vol. 22, No. 3. pp. 275-284.
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AU - Kouniavsky, Guennadi

AU - Wang, Yongchun

AU - Dackiw, Alan P B

AU - Westra, William H.

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N2 - Background: The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated "suspicious or indeterminate", but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology. Methods: Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology. Results: Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of≥0.95 (80% sensitivity; 100% specificity) and≥0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively. Conclusions: Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules.

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