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Association of Nuclear, Cytoplasmic Expression of Galectin-3 With β-Catenin/Wnt-Pathway Activation in Thyroid Carcinoma
Paul M. Weinberger, MD;
Bao-Ling Adam, PhD;
Christine G. Gourin, MD;
William H. Moretz III, MD;
Roni J. Bollag, MD, PhD;
Beverly Y. Wang, MD;
Zhongmin Liu, PhD;
Jeffrey R. Lee, MD;
David J. Terris, MD
Arch Otolaryngol Head Neck Surg. 2007;133(5):503-510.
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.
Author Affiliations: Departments of Otolaryngology (Drs Weinberger, Adam, Gourin, Moretz, Wang, and Terris) and Pathology (Drs Bollag, Wang, and Lee), Center for Biotechnology and Genomic Medicine (Drs Adam and Liu), and Institute of Molecular Medicine and Genetics (Drs Bollag and Lee), Medical College of Georgia, and Veterans Affairs Medical Center (Dr Lee), Augusta, Ga. Dr Wang is now with the Departments of Otolaryngology and Pathology, Tisch Hospital, New York University Medical Center, New York.
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