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Immunohistochemical and Molecular Markers Associated with Differentiated Thyroid Carcinoma

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초록

In the last decade, conventional diagnosis of thyroid nodules largely depended on fine-needle aspiration (FNA) and ultrasound. However, FNA has a limited ability to distinguish between benign and malignant lesions, especially in cases with indeterminate cytology. Although the clinical course of differentiated thyroid carcinoma is believed to be favorable, delayed diagnosis can make its clinical management difficult. Many immunohistochemical (IHC) or molecular adjunctive markers have been tested to improve the diagnostic accuracy for thyroid nodules. The common IHC markers galectin-3, Hector Battifora mesothelial-1, and cytokeratin-19 are used alone or as part of panels for both FNA and analysis of surgical specimens. A novel IHC marker, podoplanin, was recently introduced as an adjunctive marker for thyroid cancer diagnosis and prognosis and is associated with the progression of papillary thyroid carcinoma (PTC). Several researchers have identified molecular markers to increase the diagnostic accuracy of thyroid lesions of undetermined significance. Four promising molecular markers have been proposed and thoroughly investigated: B-type Raf kinase (BRAF) and RAS, rearranged in transformation/PTC (RET/PTC), paired box gene 8 (Pax8)/peroxisome proliferator-activated receptor gamma (PPARγ). BRAF mutations can be measured by immunohistochemistry using an antibody specific to the mutated protein. In this review, we focused on the limitations of current diagnostic tools and on determining the application of the above-mentioned markers to thyroid nodule diagnosis.

Abstract

In the last decade, conventional diagnosis of thyroid nodules largely depended on fine-needle aspiration (FNA) and ultrasound. However, FNA has a limited ability to distinguish between benign and malignant lesions, especially in cases with indeterminate cytology. Although the clinical course of differentiated thyroid carcinoma is believed to be favorable, delayed diagnosis can make its clinical management difficult. Many immunohistochemical (IHC) or molecular adjunctive markers have been tested to improve the diagnostic accuracy for thyroid nodules. The common IHC markers galectin-3, Hector Battifora mesothelial-1, and cytokeratin-19 are used alone or as part of panels for both FNA and analysis of surgical specimens. A novel IHC marker, podoplanin, was recently introduced as an adjunctive marker for thyroid cancer diagnosis and prognosis and is associated with the progression of papillary thyroid carcinoma (PTC). Several researchers have identified molecular markers to increase the diagnostic accuracy of thyroid lesions of undetermined significance. Four promising molecular markers have been proposed and thoroughly investigated: B-type Raf kinase (BRAF) and RAS, rearranged in transformation/PTC (RET/PTC), paired box gene 8 (Pax8)/peroxisome proliferator-activated receptor gamma (PPARγ). BRAF mutations can be measured by immunohistochemistry using an antibody specific to the mutated protein. In this review, we focused on the limitations of current diagnostic tools and on determining the application of the above-mentioned markers to thyroid nodule diagnosis.

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