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Objectives   To investigate the ability of cytokeratin (CK)-19, galectin-3, human bone marrow endothelial cell (HBME)-1 and tyrosine kinase-type cell surface receptor HER2 (HER-2/neu) to differentiate papillary thyroid carcinoma (PTC) from benign thyroid nodules.Methods   Archival specimens of PTC and benign thyroid nodules were included in this retrospective immunohistochemical study. CK-19, galectin-3, HBME-1, and HER-2/neu protein levels were analysed immunohistochemically using routinely prepared tissue sections.Results   Specimens from 331 patients with PTC and 664 patients with benign thyroid nodules were reviewed. For all four protein markers, the percentage of samples with cells that demonstrated positive immunostaining was significantly higher in PTC specimens than in benign thyroid nodules. As a single protein marker, CK-19 was the most sensitive (92.7%) and HBME-1 was the most specific (97.9%). The combination of CK-19 and galectin-3 was the most sensitive (82.8%), and the combinations of HBME-1 with CK-19 or galectin-3 or HER-2/neu were the most specific (98.3%).Conclusions   The combination of HBME-1 and either CK19 or galectin-3 or HER-2/neu can improve the specificity of the diagnosis of PTC.

Combined staining for immunohistochemical markers in the diagnosis of papillary thyroid carcinoma: Improvement in the sensitivity or specificity?