Association of nuclear, cytoplasmic expression of galectin-3 with β-catenin/Wnt-pathway activation in thyroid carcinoma

Objectives: To characterize the localization of galectin-3 in benign and malignant thyroid neoplasms and to correlate this with alterations in β-catenin and cyclin D1 expression. Design: Immunohistochemical study of 116 paraffin-embedded archival specimens from 113 patients who had undergone thyroidectomy and tissue placed into a commercially available tissue microarray. Setting: Tertiary care hospital. Interventions: Thyroid tissue microarrays were stained by standard immunohistochemical protocols with monoclonal antibodies against galectin-3, β-catenin, and cyclin D1. Main Outcome Measures: Nuclear and cytoplasmic expression of galectin-3 was correlated with clinical parameters, β-catenin, and cyclin D1 expression. Results: Both cytoplasmic (56%) and nuclear (42%) galectin-3 expression was observed in most malignant neoplasms but was absent in benign thyroid specimens (P<.001). Among carcinomas, cytoplasmic galectin-3 expression was observed in papillary thyroid carcinomas (82%) and follicular (33%) and medullary (9%) carcinomas but was absent in anaplastic carcinomas (P<.001). Galectin-3 nuclear expression was observed in papillary thyroid carcinomas (62%) and follicular carcinomas (33%) but was undetectable in medullary, anaplastic carcinomas (P<.001). Cytoplasmic but not nuclear galectin-3 was inversely correlated with American Joint Committee on Cancer TNM stage (P=.02). There was a strong correlation between cytoplasmic and nuclear β-catenin expression and both nuclear (P=.04) and cytoplasmic (P=.003) galectin-3 expression. Similarly, there was a strong association between galectin-3 nuclear (P<.001) and cytoplasmic (P<.001) expression and cyclin D1 expression. Conclusion: Cytoplasmic and nuclear galectin-3 expression seem to be associated with activation of the Wnt-signaling pathway in well-differentiated thyroid neoplasms, suggesting that galectin-3 plays a role in thyroid carcinogenesis.