Universal Markers of Thyroid Malignancies: Galectin-3, HBME-1, and Cytokeratin-19

Abstract

Difficulties in diagnosis of thyroid lesions, even with histologic analysis, are well known. This study has been carried on to evaluate the role of immunohistochemical markers including galectin-3, Hector Battifora mesothelial cell-1 (HBME-1), and cytokeratin-19 in the diagnosis and differential diagnosis of benign and malignant thyroid lesions. The expressions of galectin-3, HBME-1, and cytokeratin-19 were tested in formalin-fixed, paraffin-embedded tissues from 458 surgically resected thyroid lesions including non-neoplastic and neoplastic lesions. Immunostaining with standard avidin-biotin complex technique was performed by using monoclonal antibodies. In malignant neoplastic thyroid lesions, galectin-3, HBME-1, and cytokeratin-19 were diffusely expressed in general. Diffuse expression rates of these three markers were 72.3% (47/65), 70.7% (46/65), and 76.9% (50/65), respectively. The use of galectin-3, HBME-1, and cytokeratin-19 may provide significant contributions in the differential diagnosis of malignant thyroid tumors. Although focal galectin-3, HBME-1, and cytokeratin-19 expression may be encountered in benign lesions, diffuse positive reactions for these three markers are characteristic of malignant lesions. It has concluded that cytokeratin-19 alone and its combinations with other markers were more sensitive in accurate diagnosis of papillary carcinoma than the other combinations; meanwhile, there were similar results for follicular carcinomas with HBME-1 alone and its combinations.

Diagnostic value of TROP-2 expression in papillary thyroid carcinoma and comparison with HBME-1, galectin-3 and cytokeratin 19

“…In our study, these ratios were respectively 83.3% and 60% for distinguishing FND-FA and PTC, and 70% and 60% for distinguishing FND-FA and FVPTC. In agreement with the literature [4,8], we observed that usage of CK19 by itself had the highest sensitivity as a marker in distinguishing benign lesions from PTC and FVPTC (83.3%, 70%). However, its specificity was lower due to its positivity in benign lesions (60%).…”

“…CK19 is a low molecular weight cytokeratin which is expressed in various epithelial tissues and tumors [10]. While there are differences among studies in terms of the extensiveness and intensity of its expression in follicular epithelial cell derived lesions of the thyroid, it is more diffused and stronger in papillary carcinoma [5,8,9,10]. Additionally, it is known to be positively stained also in benign nodules and follicular adenoma [7,8].…”

“…HBME-1 is a monoclonal antibody developed against the antigen on the microvillous surface of human mesothelial cells [20]. There are numerous studies reporting its advantages in determining malignancy in thyroid nodules derived from follicular epithelial cells [5,8,10,21]. Moreover, there are also studies showing HBME-1 as positive in benign thyroid lesions such as chronic lymphocytic thyroiditis, benign thyroid nodules and follicular adenoma [7,9,22].…”

“…Correct pathological diagnosis is necessary to minimize emotional stress, over-treatments and related financial costs brought by the diagnosis of thyroid cancer [3]. In order to eliminate disagreements among pathologists about well-differentiated lesions of thyroid derived from follicular epithelial cells and achieve diagnostic standardization, there have been many studies made where immunohistochemical and molecular markers are studied [4,5,6,7,8,9,10,11,12]. The immunohistochemical markers Hector Battifora mesothelial cell epitope-1 (HBME-1), galectin 3 (Gal-3) and cytokeratin 19 (CK19) accepted to be indicators of malignancy in thyroid lesions have been used as products of such studies as panels in most pathology laboratories.…”

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

“…Further studies showed that the expression level of CK19 or CK19 fragments differ in various subtypes of thyroid tumors (Raphael et al 1994, Miettinen et al 1997. Most studies demonstrated that overexpression of CK19 is mainly related to papillary thyroid cancer with a positive rate, accounting for 70-100% of all cancers (Flanagan et al 2008, Krzeslak et al 2008, Barut et al 2010, Gong et al 2012. Furthermore, CK19 has been used in combination with PAX8 and HBME1 to increase the specificity of diagnosis for thyroid tumors by FNA (Schmitt et al 2010, Cochand-Priollet et al 2011.…”