The Diagnostic Usefulness of HMGA2, Survivin, CEACAM6, and SFN/14-3-3 δ in Follicular Thyroid Carcinoma

Follicular thyroid carcinoma (FTC) is the second most common thyroid malignancy with a reported incidence of 5%–20% [1]. Its preoperative diagnosis is not possible, as FTC can only be diagnosed in a surgically-resected specimen [2,3]. However, the differential diagnosis between FTC, follicular adenoma (FA), and adenomatous goiter (AG) is often difficult, even in resected lesions. Occasionally AG has a fibrous capsule and solid proliferation of follicles, requiring detailed microscopic examination for its diagnosis [4,5]. The distinction between benign and malignant follicular-patterned lesions solely depends on the presence of capsular and/or vascular invasion [4-7]. Therefore, all patients with follicular neoplasm (FN) diagnosed with fine needle aspiration are recommended to undergo a thyroid lobectomy for histologic confirmation [2]. If the tumor is diagnosed as FTC, additional resection of the remaining thyroid or lymph node is required. Previous studies have reported differential expression of several genes in malignant neoplasms, and the use of some of those markers for differential diagnosis has been subsequently validated in formalin-fixed paraffin-embedded (FFPE) tissues [8-15]. DDIT3, ARG2, ITM1, and C1orf24 have been tested as additional diagnostic tools for distinguishing FTC from FA, but none have been proven to be reliable markers [16,17]. CEACAM6, HMGA2, and SFN/14-3-3 δ (stratifin) need to be validated using FFPE thyroid tissues. Additionally, it has been suggested that the expression of survivin is higher in FTC than in FA, but the number of cases was limited in the study (FTC, 11 cases)[11]. Galectin 3 (Gal-3), Hector Battifora mesothelial 1 (HBME1), cytokeratin 19 (CK19), and cyclin D1, all of which are well-established diagnostic markers for papillary thyroid carcinoma (PTC), have also been used in differentiating FTC from other benign follicular lesions but the results are controversial [15,18-20]. In the present study, we evaluated the immunohistochemical expression of HMGA2, CEACAM6, survivin, SFN/14-3-3 δ, Gal-3, HBME1, CK19, and cyclin D1 in lesions including 41 AGs, 72 FAs, and 79 FTCs. We also evaluated their diagnostic usefulness in differentiating FTC.