Diagnostic Value of Galectin-3, HBME-1, Cytokeratin 19, High Molecular Weight Cytokeratin, Cyclin D1 and p27kip1 in the Differential Diagnosis of Thyroid Nodules

Abstract

The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27kip1 in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC).The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.

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

“…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]. In Cheung et al's study, 80% of CVPTCs, 57% of FVPTCs, and 20% of nodular hyperplasia and FAs were positive with CK19 [5].…”

“…It is also stained in reactive epithelial cells and inflammatory cells [22]. There are many studies demonstrating the positivity of Gal-3 in malignant lesions of thyroid, especially CVPTC [7,8,9,10,22]. Furthermore, positivity with varying frequencies was reported in different studies in benign thyroid nodules and lesions, follicular adenoma and FVPTC [7,8,9,10,12,22].…”

“…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]. While Cheung et al did not find positivity with HBME-1 in any of the benign thyroid nodules and cases of follicular adenoma, they found positivity in 55% of cases with papillary carcinoma, 70% in CVPTC, and only 45% in FVPTC [5].…”

“…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.…”

Paired box gene 8, HBME‐1, and cytokeratin 19 expression in preoperative fine‐needle aspiration of papillary thyroid carcinoma

“…12,13 In the same study, it was deemed nonspecific because it also stained 68.4% of BTN cases, findings confirmed by other authors. 13,18 Although CK19 may focally stain benign lesions, diffuse and strong staining is considered typical of PTC, with a proposed cutoff value of !10% immunoreactive cells to differentiate carcinomas from adenomas. 11,16,17 The combination of HBME-1 and CK19 has been proposed to demonstrate the highest diagnostic value for the differential diagnosis of PTC, with specificity values for the diagnosis of PTC of up to 100% when coexpression of HBME-1 and CK19 is demonstrated.…”