J Korean Thyroid Assoc.  2015 May;8(1):50-60. 10.11106/cet.2015.8.1.50.

Immunohistochemical and Molecular Markers Associated with Differentiated Thyroid Carcinoma

• Jung JW
• Choi JY
• Lee KE
• Park KW

• KMID: 2149620
• DOI: http://doi.org/10.11106/cet.2015.8.1.50

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 (PPARgamma). 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.

Keyword

Differentiated thyroid carcinoma; Immunohistochemistry; Molecular markers

MeSH Terms

Biopsy, Fine-Needle
Delayed Diagnosis
Diagnosis
Galectin 3
Immunohistochemistry
Keratin-19
Phosphotransferases
Prognosis
Thyroid Gland
Thyroid Neoplasms*
Thyroid Nodule
Ultrasonography
Galectin 3
Keratin-19
Phosphotransferases

Figure

• 

  Fig. 1. Galectin-3 immunostaining. (A) Galectin-3 is diffusely expressed in papillary thyroid carcinoma. It is localized in both the cytoplasm and nuclei (×400). (B) Focal expression of galectin-3 is detected in follicular thyroid carcinoma (×200). (C) Galectin-3 is not detected in follicular adenoma (×200).

• 

  Fig. 2. HBME-1 immunostaining. (A) Papillary thyroid carcinoma exhibits a strong membranous staining (×200). (B) Follicular thyroid carcinoma exhibits a diffuse cytoplasmic staining (×200). (C) Follicular adenoma shows focal expression of HBME-1 (×200).

• 

  Fig. 3. CK-19 immunostaining. (A) Papillary thyroid carcinoma exhibits a diffuse expression of CK-19 (×200). (B) Focal expression of CK19 is detected in follicular thyroid carcinoma (×200). (C) CK-19 is not detected in follicular adenoma (×200).

• 

  Fig. 4. BRAF staining in papillary thyroid carcinoma. A diffuse expression can be distinctively observed in both the cytoplasm and nuclei (×200).

Reference

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