Utility of Immunohistochemistry Markers CK19, Gal-3, HBME-1 and Their Combinations for Differential Diagnosis of Thyroid Diseases

Abstract

Differential diagnosis is important for clinical management of cases with thyroid diseases. We aimed to find the most useful diagnostic panel including immunohistochemistry markers and BRAF 600E mutation for papillary thyroid carcinoma. The study included 99 papillary thyroid carcinoma, 95 benign thyroid disease and 6 well differentiated tumour of uncertain malignant potential cases. Three groups were compared for immunohistochemistry marker expressions (CK19, Gal-3, HBME-1, p63, CD56). Diagnostic contribution of BRAF V600E mutation and its relationship with the immunohistochemistry and prognostic parameters were evaluated. CK19, Gal-3, HBME-1 and p63 positivity and loss of CD56 expression were significantly higher in papillary thyroid carcinoma than in benign thyroid disease. Gal-3 was the most useful marker to differentiate both papillary thyroid carcinoma and well-differentiated tumour of uncertain malignant potential cases from benign thyroid disease. CK19&HBME-1 and CK19&-Gal-3 dual panels had the highest sensitivities and high specificities for distinguishing papillary thyroid carcinoma from benign thyroid disease. Moreover, CK19&Gal-3 dual panel had the highest sensitivity and specificity to distinguish well-differentiated tumour of uncertain malignant potential from benign thyroid disease. In addition, CK19&Gal-3&HBME-1 was the most sensitive triple panel in differentiating both papillary thyroid carcinoma and well-differentiated tumour of uncertain malignant potential cases from benign thyroid disease. When combined with immunohistochemistry markers, the BRAF V600E reduced sensitivities and increased specificities towards malignancy, and it was not associated with prognostic parameters except for histological subtypes.