Atypical thyroid nodules express both HBME-1 and Galectin-3, two phenotypic markers of papillary thyroid carcinoma.

Ninety-six thyroid lesions were immunohistochemically evaluated for HBME-1 and Galectin-3 expression including nodules with cytological atypia, the latter defined as nuclear features suggestive but not diagnostic of papillary thyroid carcinoma. Thirty nodules with cytological atypia, 49 papillary thyroid carcinomas (PTCs), 4 follicular carcinomas and 13 oxyphilic tumors were examined. Forty-one of the 49 PTCs, 16 atypical thyroid nodules and 3 non-malignant oxyphilic tumors exhibited a combined expression of HBME-1 and Galectin-3. In 6 of the sixteen atypical thyroid nodules the immunoreactivity for both markers was strong and diffuse, simulating the pattern observed in PTC. We conclude that thyroid nodules with cytological atypia and strong/diffuse positivity for both HBME-1 and Galectin-3, two well recognized markers of PTC, represent a starting phenotypic change towards PTC, for which a benign or borderline counterpart has not yet been defined. The expression of HBME-1 and Galectin-3 in some thyroid nodules is related to the presence of cytological atypia suggestive but not diagnostic of PTC. The phenotypic similarity between this subset of thyroid nodules with cytological atypia and PTC is also confirmed by our data according to which Galectin-3 and HBME-1 have been found to be highly sensitive for PTC.