Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms P Mehrotra, 1 A Okpokam, 2 R Bouhaidar, 2 S J Johnson, 2 J A Wilson, 1,3 B R Davies 1 & T W J Lennard 1,4 1 School of Surgical and Reproductive Sciences, University of Newcastle upon Tyne, 2 Department of Cellular Pathology, Royal Victoria Infirmary, 3 Department of Otorhinolaryngology, Freeman Hospital, and 4 Department of Surgery, Royal Victoria Infirmary, Newcastle upon Tyne, UK Date of submission 18 February 2004 Accepted for publication 15 April 2004 Mehrotra P, Okpokam A, Bouhaidar R, Johnson S J, Wilson J A, Davies B R & Lennard T W J (2004) Histopathology 45, 493–500 Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms Aims: To determine whether galectin-3 is a sensitive indicator of thyroid malignancy. It has been suggested as a potential marker for differentiating thyroid carcin- oma from benign or non-neoplastic lesions in preoper- ative fine-needle aspirates (FNAs). Methods: Galectin-3 protein expression was assessed by immunohistochemistry in formalin-fixed thyroid tis- sues from 124 patients with histological diagnoses of papillary carcinoma (n ¼ 38), follicular carcinoma (n ¼ 19), follicular adenoma (n ¼ 32) and dominant nodules of multinodular goitre (n ¼ 35). Expression of galectin-3 was also assessed by Western blotting in 24 fresh thyroid tissues. Results: Galectin-3 expression was observed in the majority of carcinomas (papillary 92%; follicular 74%). However, a large proportion of follicular adenomas (72%) and multinodular goitres (57%) also expressed galectin-3. In addition, galectin-3 expression was observed in epithelial cells of normal thyroid tissue and Hashimoto’s thyroiditis. Galectin-3 immunoposi- tivity was significantly greater in papillary carcinomas than in dominant nodules or follicular adenomas (P< 0.0001, P ¼ 0.0005, respectively). However, galectin-3 expression was no greater in follicular carcinomas than in follicular adenomas (P ¼ 0.8735). Western blotting analysis confirmed both the specificity of the antiserum and expression of galectin-3 in multinodular goitres, follicular aden- omas ⁄ carcinomas and papillary carcinomas. Conclusion: The data demonstrate that galectin-3 is not a reliable immunohistochemical marker to distinguish benign from malignant thyroid follicular lesions. Keywords: follicular adenoma, follicular carcinoma, galectin-3, immunohistochemistry, papillary carcinoma, thyroid Abbreviation: FNA, fine-needle aspirate ⁄ aspiration Introduction Solitary thyroid nodules are a common condition, affecting 3.2% of the non-iodine-deficient population. 1 The best investigation available at present to assess the nature of a thyroid nodule preoperatively is fine-needle aspiration (FNA) cytology. The major limitation of FNA is that it cannot differentiate between various follicular lesions, including hyperplastic nodules, but most par- ticularly between follicular adenoma and follicular carcinoma because they can only be distinguished by assessing for vascular and ⁄ or capsular invasion on a histological specimen. A few markers have been proposed to potentially differentiate follicular adenoma from its malignant counterpart preoperatively. Several studies have suggested galectin-3, a 31-kDa b-galactoside-binding lectin, as one such marker. 2–11 Galectin-3 contains two distinct domains: an amino terminal half with proline- and glycine-rich tandem Address for correspondence: Dr B R Davies, Northern Institute for Cancer Research, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK. e-mail: b.r.davies@ncl.ac.uk Ó 2004 Blackwell Publishing Limited. Histopathology 2004, 45, 493–500