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Paul C. Bryson, MD; Carol G. Shores, MD, PhD; Craig Hart, MD; Leigh Thorne, MD; Mihir R. Patel, MD; Luke Richey, BS; Alexander Farag, BA; Adam M. Zanation, MD

Arch Otolaryngol Head Neck Surg. 2008;134(6):581-586.

Objectives  To use immunohistochemical (IHC) evaluation of proteins encoded by genes that were differentially expressed in follicular thyroid adenomas (FAs) vs follicular thyroid carcinomas (FTCs) to distinguish benign vs malignant follicular thyroid lesions. Multiple gene microarray studies suggest that benign and malignant follicular thyroid neoplasms have different gene expression profiles.

Design  Immunohistochemical analysis of thyroid neoplasms, including FA (n = 62), FTC (n = 62), and follicular variant of papillary thyroid carcinoma (n = 58), using tissue microarrays. We evaluated antibodies galectin-3, autotaxin, intestinal trefoil factor 3 (TFF3), extracellular matrix metalloproteinase inducer (EMMPRIN), and growth arrest and DNA damage-inducible protein 153 (GADD153). We analyzed data for quantitative differences in IHC intensity and the percentage of positive cells between FAs and combined follicular carcinomas. Sensitivity and specificity analysis are reported, along with a dual-protein clinical algorithm.

Setting  Academic tertiary care center.

Patients  Adults with known follicular and papillary thyroid lesions that were surgically resected during the past 15 years.

Main Outcome Measures  Sensitivity and specificity of individual and combined antibodies for detecting benign from malignant lesions.

Results  Quantitative analysis showed IHC validation of the gene expression differences noted in previously published microarray reports. A significantly higher percentage of FTC cells stained with galectin-3, EMMPRIN, and GADD153. Galectin-3 and EMMPRIN also showed a significantly higher intensity of staining in FTC cells. Compared with malignant lesions, TFF3 stained a greater cell percentage in FAs. Galectin-3 (sensitivity, 0.72; specificity, 0.62) and EMMPRIN (sensitivity, 0.63; specificity, 0.49) had the most promising diagnostic potential with a dual-protein sensitivity of 0.80 and specificity of 0.70. Autotaxin and GADD153 had overall higher sensitivities (0.88 and 0.82, respectively) but very poor specificities (0.02 and 0.21, respectively).

Conclusions  Protein expression data validate the pooled gene expression results that differentiate FTC from FA. Our results show promise for multiple-protein IHC analysis algorithms and their diagnostic ability. Future studies should focus on clinical translation of these molecular differences for the diagnosis of follicular thyroid neoplasms.

Author Affiliations: Departments of Otolaryngology–Head and Neck Surgery (Drs Bryson, Shores, Patel, and Zanation) and Pathology and Laboratory Medicine (Drs Hart and Thorne), Lineberger Comprehensive Cancer Center (Drs Shores and Thorne), and School of Medicine (Messrs Richey and Farag), University of North Carolina Hospitals, Chapel Hill.