Diagnostic Utility of Galectin-3 in Thyroid Cancer

The American Journal of Pathology - Tập 176 - Trang 2067-2081 - 2010
Connie G. Chiu1, Scott S. Strugnell1, Obi L. Griffith2, Steven J.M. Jones2, Allen M. Gown3,4, Blair Walker5, Ivan R. Nabi6, Sam M. Wiseman1
1Department of Surgery, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
2Department of Medical Genetics, University of British Columbia and Michael Smith Genome Sciences Center, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
3Department of Pathology, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
4PhenoPath Laboratories, Seattle, Washington
5Department of Laboratory Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
6Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada

Tài liệu tham khảo

Gharib, 2007, Thyroid nodules: clinical importance, assessment, and treatment, Endocrinol Metab Clin North Am, 36, 707, 10.1016/j.ecl.2007.04.009 Gharib, 1994, Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and effect, Mayo Clin Proc, 69, 44, 10.1016/S0025-6196(12)61611-5 Wiseman, 2006, Hemithyroidectomy: the optimal initial surgical approach for individuals undergoing surgery for a cytological diagnosis of follicular neoplasm, Ann Surg Oncol, 13, 425, 10.1245/ASO.2006.03.089 Melck, 2006, Hemithyroidectomy: the preferred initial surgical approach for management of Hurthle cell neoplasm, Am J Surg, 191, 593, 10.1016/j.amjsurg.2006.02.007 Cooper, 2006, Management guidelines for patients with thyroid nodules and differentiated thyroid cancer, Thyroid, 16, 109, 10.1089/thy.2006.16.109 Wiseman, 2008, Molecular phenotyping of thyroid tumors identifies a marker panel for differentiated thyroid cancer diagnosis, Ann Surg Oncol, 15, 2811, 10.1245/s10434-008-0034-8 Barondes, 1994, Galectins: a family of animal beta-galactoside-binding lectins, Cell, 76, 597, 10.1016/0092-8674(94)90498-7 Hsu, 1992, Biochemical and biophysical characterization of human recombinant IgE-binding protein, an S-type animal lectin, J Biol Chem, 267, 14167, 10.1016/S0021-9258(19)49693-2 Mehul, 1995, Cross-linking of galectin 3, a galactose-binding protein of mammalian cells, by tissue-type transglutaminase, FEBS Lett, 360, 160, 10.1016/0014-5793(95)00100-N Ahmad, 2004, Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates and forms heterogeneous cross-linked complexes, J Biol Chem, 279, 10841, 10.1074/jbc.M312834200 Liu, 2005, Galectins as modulators of tumour progression, Nat Rev Cancer, 5, 29, 10.1038/nrc1527 Dumic, 2006, Galectin-3: an open-ended story, Biochim Biophys Acta, 1760, 616, 10.1016/j.bbagen.2005.12.020 Ramasamy, 2007, The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop, Mol Cell, 27, 992, 10.1016/j.molcel.2007.07.031 Nieminen, 2007, Visualization of galectin-3 oligomerization on the surface of neutrophils and endothelial cells using fluorescence resonance energy transfer, J Biol Chem, 282, 1374, 10.1074/jbc.M604506200 Partridge, 2004, Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis, Science, 306, 120, 10.1126/science.1102109 Lajoie, 2007, Plasma membrane domain organization regulates EGFR signaling in tumor cells, J Cell Biol, 179, 341, 10.1083/jcb.200611106 Gong, 1999, The NH2 terminus of galectin-3 governs cellular compartmentalization and functions in cancer cells, Cancer Res, 59, 6239 Xu, 1995, Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications, Am J Pathol, 147, 815 Yang, 1996, Expression of galectin-3 modulates T-cell growth and apoptosis, Proc Natl Acad Sci USA, 93, 6737, 10.1073/pnas.93.13.6737 Paron, 2003, Nuclear localization of Galectin-3 in transformed thyroid cells: a role in transcriptional regulation, Biochem Biophys Res Commun, 302, 545, 10.1016/S0006-291X(03)00151-7 Lin, 2009, Galectin-3 regulates apoptosis and doxorubicin chemoresistance in papillary thyroid cancer cells, Biochem Biophys Res Commun, 379, 626, 10.1016/j.bbrc.2008.12.153 Shi, 2007, Inhibition of Wnt-2 and galectin-3 synergistically destabilizes beta-catenin and induces apoptosis in human colorectal cancer cells, Int J Cancer, 121, 1175, 10.1002/ijc.22848 Akahani, 1997, Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family, Cancer Res, 57, 5272 Yu, 2002, Galectin-3 translocates to the perinuclear membranes and inhibits cytochrome c release from the mitochondria. A role for synexin in galectin-3 translocation, J Biol Chem, 277, 15819, 10.1074/jbc.M200154200 Cecchinelli, 2006, Repression of the antiapoptotic molecule galectin-3 by homeodomain-interacting protein kinase 2-activated p53 is required for p53-induced apoptosis, Mol Cell Biol, 26, 4746, 10.1128/MCB.00959-05 Lavra, 2009, Gal-3 is stimulated by gain-of-function p53 mutations and modulates chemoresistance in anaplastic thyroid carcinomas, J Pathol, 218, 66, 10.1002/path.2510 Fukumori, 2004, Endogenous galectin-3 determines the routing of CD95 apoptotic signaling pathways, Cancer Res, 64, 3376, 10.1158/0008-5472.CAN-04-0336 Liu, 2004, Nucling mediates apoptosis by inhibiting expression of galectin-3 through interference with nuclear factor kappaB signalling, Biochem J, 380, 31, 10.1042/bj20031300 Takenaka, 2003, Malignant transformation of thyroid follicular cells by galectin-3, Cancer Lett, 195, 111, 10.1016/S0304-3835(03)00056-9 Bresalier, 1998, Metastasis of human colon cancer is altered by modifying expression of the beta-galactoside-binding protein galectin 3, Gastroenterology, 115, 287, 10.1016/S0016-5085(98)70195-7 van den Brule, 2004, Expression of galectins in cancer: a critical review, Glycoconj J, 19, 537, 10.1023/B:GLYC.0000014083.48508.6a Davidson, 2002, Shuttling of galectin-3 between the nucleus and cytoplasm, Glycobiology, 12, 329, 10.1093/glycob/12.5.329 Yoshii, 2002, Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest, J Biol Chem, 277, 6852, 10.1074/jbc.M107668200 Takenaka, 2004, Galectin-3 and metastasis, Glycoconj J, 19, 543, 10.1023/B:GLYC.0000014084.01324.15 Califice, 2004, Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3, Oncogene, 23, 7527, 10.1038/sj.onc.1207997 Dennis, 1989, Oncodevelopmental expression of–GlcNAc beta 1–6Man alpha 1–6Man beta 1–branched asparagine-linked oligosaccharides in murine tissues and human breast carcinomas, Cancer Res, 49, 945 Miyoshi, 1995, Transforming growth factor beta up-regulates expression of the N-acetylglucosaminyltransferase V gene in mouse melanoma cells, J Biol Chem, 270, 6216, 10.1074/jbc.270.11.6216 Yao, 1998, Elevated activity of N-acetylglucosaminyltransferase V in human hepatocellular carcinoma, J Cancer Res Clin Oncol, 124, 27, 10.1007/s004320050129 Murata, 2000, Expression of N-acetylglucosaminyltransferase V in colorectal cancer correlates with metastasis and poor prognosis, Clin Cancer Res, 6, 1772 Fernandes, 1991, Beta 1-6 branched oligosaccharides as a marker of tumor progression in human breast and colon neoplasia, Cancer Res, 51, 718 Granovsky, 2000, Suppression of tumor growth and metastasis in Mgat5-deficient mice, Nat Med, 6, 306, 10.1038/73163 Lau, 2007, Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation, Cell, 129, 123, 10.1016/j.cell.2007.01.049 Lagana, 2006, Galectin binding to Mgat5-modified N-glycans regulates fibronectin matrix remodeling in tumor cells, Mol Cell Biol, 26, 3181, 10.1128/MCB.26.8.3181-3193.2006 Goetz, 2008, Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1, J Cell Biol, 180, 1261, 10.1083/jcb.200709019 Dennis, 2009, Adaptive regulation at the cell surface by N-glycosylation, Traffic, 10, 1569, 10.1111/j.1600-0854.2009.00981.x Lajoie, 2009, Lattices, rafts, and scaffolds: domain regulation of receptor signaling at the plasma membrane, J Cell Biol, 185, 381, 10.1083/jcb.200811059 Griffith, 2008, Biomarker panel diagnosis of thyroid cancer: a critical review, Expert Rev Anticancer Ther, 8, 1399, 10.1586/14737140.8.9.1399 Orlandi, 1998, Galectin-3 is a presurgical marker of human thyroid carcinoma, Cancer Res, 58, 3015 Gasbarri, 1999, Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules, J Clin Oncol, 17, 3494, 10.1200/JCO.1999.17.11.3494 Inohara, 1999, Expression of galectin-3 in fine-needle aspirates as a diagnostic marker differentiating benign from malignant thyroid neoplasms, Cancer, 85, 2475, 10.1002/(SICI)1097-0142(19990601)85:11<2475::AID-CNCR25>3.0.CO;2-1 Bartolazzi, 2001, Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions, Lancet, 357, 1644, 10.1016/S0140-6736(00)04817-0 Saggiorato, 2001, Galectin-3 as a presurgical immunocytodiagnostic marker of minimally invasive follicular thyroid carcinoma, J Clin Endocrinol Metab, 86, 5152, 10.1210/jcem.86.11.8043 Aratake, 2002, Diagnostic utility of galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules, Diagn Cytopathol, 26, 366, 10.1002/dc.10111 Papotti, 2002, Role of galectin-3 immunodetection in the cytological diagnosis of thyroid cystic papillary carcinoma, Eur J Endocrinol, 147, 515, 10.1530/eje.0.1470515 Maruta, 2004, Immunostaining of galectin-3 and CD44v6 using fine-needle aspiration for distinguishing follicular carcinoma from adenoma, Diagn Cytopathol, 31, 392, 10.1002/dc.20156 Saggiorato, 2004, Galectin-3: presurgical marker of thyroid follicular epithelial cell-derived carcinomas, J Endocrinol Invest, 27, 311, 10.1007/BF03351054 Collet, 2005, Galectin-3 immunodetection in follicular thyroid neoplasms: a prospective study on fine-needle aspiration samples, Br J Cancer, 93, 1175, 10.1038/sj.bjc.6602822 Mills, 2005, Galectin-3 is not useful in thyroid FNA, Cytopathology, 16, 132, 10.1111/j.1365-2303.2005.00213.x Saggiorato, 2005, Characterization of thyroid ‘follicular neoplasms’ in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application, Endocr Relat Cancer, 12, 305, 10.1677/erc.1.00944 Aron, 2006, Utility of galectin 3 expression in thyroid aspirates as a diagnostic marker in differentiating benign from malignant thyroid neoplasms, Indian J Pathol Microbiol, 49, 376 Carpi, 2006, Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology, Br J Cancer, 95, 204, 10.1038/sj.bjc.6603232 Kim, 2006, Diagnostic utility of galectin-3 in aspirates of thyroid follicular lesions, Acta Cytol, 50, 28, 10.1159/000325891 Torres-Cabala, 2006, Proteomic identification of new biomarkers and application in thyroid cytology, Acta Cytol, 50, 518, 10.1159/000326006 Sapio, 2007, Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma, Endocr Relat Cancer, 14, 1089, 10.1677/ERC-07-0147 Hooft, 2008, Hexokinase III, cyclin A and galectin-3 are overexpressed in malignant follicular thyroid nodules, Clin Endocrinol (Oxf), 68, 252, 10.1111/j.1365-2265.2007.03031.x Ersoz, 2008, The significance of Galectin-3 expression in the immunocytochemical evaluation of thyroid fine needle aspiration cytology, Pathol Oncol Res, 14, 457, 10.1007/s12253-008-9041-0 Bartolazzi, 2008, Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study, Lancet Oncol, 9, 543, 10.1016/S1470-2045(08)70132-3 Franco, 2009, Molecular markers in thyroid fine-needle aspiration biopsy: a prospective study, Appl Immunohistochem Mol Morphol, 17, 211, 10.1097/PAI.0b013e31818935a9 Fernandez, 1997, Galectin-3 and laminin expression in neoplastic and non-neoplastic thyroid tissue, J Pathol, 181, 80, 10.1002/(SICI)1096-9896(199701)181:1<80::AID-PATH699>3.0.CO;2-E Cvejic, 2000, Galectin-3 and carcinoembryonic antigen expression in medullary thyroid carcinoma: possible relation to tumour progression, Histopathology, 37, 530, 10.1046/j.1365-2559.2000.00988.x Kawachi, 2000, Galectin-3 expression in various thyroid neoplasms and its possible role in metastasis formation, Hum Pathol, 31, 428, 10.1053/hp.2000.6534 Nascimento, 2001, Differential reactivity for galectin-3 in Hurthle cell adenomas and carcinomas, Endocr Pathol, 12, 275, 10.1385/EP:12:3:275 Beesley, 2002, Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules, Histopathology, 41, 236, 10.1046/j.1365-2559.2002.01442.x Coli, 2002, Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia, Histopathology, 40, 80, 10.1046/j.1365-2559.2002.01304.x Faggiano, 2002, Differential expression of galectin-3 in medullary thyroid carcinoma and C-cell hyperplasia, Clin Endocrinol (Oxf), 57, 813, 10.1046/j.1365-2265.2002.01673.x Herrmann, 2002, Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions, Arch Pathol Lab Med, 126, 710, 10.5858/2002-126-0710-IEOGIB Casey, 2003, Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1, Endocr Pathol, 14, 55, 10.1385/EP:14:1:55 Feilchenfeldt, 2003, Expression of galectin-3 in normal and malignant thyroid tissue by quantitative PCR and immunohistochemistry, Mod Pathol, 16, 1117, 10.1097/01.MP.0000096047.99202.31 Giannini, 2003, Galectin-3 and oncofetal-fibronectin expression in thyroid neoplasia as assessed by reverse transcription-polymerase chain reaction and immunochemistry in cytologic and pathologic specimens, Thyroid, 13, 765, 10.1089/105072503768499662 Kovacs, 2003, The investigation of galectin-3 in diseases of the thyroid gland, Eur J Endocrinol, 149, 449, 10.1530/eje.0.1490449 Mehrotra, 2004, Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms, Histopathology, 45, 493, 10.1111/j.1365-2559.2004.01978.x Oestreicher-Kedem, 2004, Diagnostic value of galectin-3 as a marker for malignancy in follicular patterned thyroid lesions, Head Neck, 26, 960, 10.1002/hed.20087 Weber, 2004, The use of a combination of galectin-3 and thyroid peroxidase for the diagnosis and prognosis of thyroid cancer, Am J Clin Pathol, 122, 524, 10.1309/UUQTE505PTN5QJ7M de Matos, 2005, Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy, Histopathology, 47, 391, 10.1111/j.1365-2559.2005.02221.x Ito, 2005, Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma, Pathology, 37, 296, 10.1080/00313020500169545 Nucera, 2005, Human galectin-3 immunoexpression in thyroid follicular adenomas with cell atypia, J Endocrinol Invest, 28, 106, 10.1007/BF03345351 Prasad, 2005, Galectin-3, fibronectin-1. CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors, Mod Pathol, 18, 48, 10.1038/modpathol.3800235 Cvejic, 2005, Galectin-3 expression in papillary thyroid carcinoma: relation to histomorphologic growth pattern, lymph node metastasis, extrathyroid invasion, and tumor size, Head Neck, 27, 1049, 10.1002/hed.20276 Cvejic, 2005, Galectin-3 and proliferating cell nuclear antigen (PCNA) expression in papillary thyroid carcinoma, Exp Oncol, 27, 210 Aratake, 2006, Coexistent anaplastic and differentiated thyroid carcinoma: an immunohistochemical study, Am J Clin Pathol, 125, 399, 10.1309/LF3Q1NQKMT2N9KNV Barroeta, 2006, Diagnostic value of differential expression of CK19. Galectin-3, HBME-1, ERK, RET, and p16 in benign and malignant follicular-derived lesions of the thyroid: an immunohistochemical tissue microarray analysis, Endocr Pathol, 17, 225, 10.1385/EP:17:3:225 Nakamura, 2006, Immunohistochemical separation of follicular variant of papillary thyroid carcinoma from follicular adenoma, Endocr Pathol, 17, 213, 10.1385/EP:17:3:213 Rossi, 2006, Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid, Histopathology, 48, 795, 10.1111/j.1365-2559.2006.02428.x Scognamiglio, 2006, Diagnostic usefulness of HBME1, galectin-3. CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma, Am J Clin Pathol, 126, 700, 10.1309/044V86JN2W3CN5YB Coli, 2007, Atypical thyroid nodules express both HBME-1 and Galectin-3, two phenotypic markers of papillary thyroid carcinoma, J Exp Clin Cancer Res, 26, 221 Park, 2007, Diagnostic value of galectin-3. HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27(kip1) in the differential diagnosis of thyroid nodules, J Korean Med Sci, 22, 621, 10.3346/jkms.2007.22.4.621 Pulcrano, 2007, Poorly differentiated follicular thyroid carcinoma: prognostic factors and relevance of histological classification, Thyroid, 17, 639, 10.1089/thy.2007.0029 Torregrossa, 2007, Galectin-3 is highly expressed in nonencapsulated papillary thyroid carcinoma but weakly expressed in encapsulated type; comparison with Hector Battifora mesothelial cell 1 immunoreactivity, Hum Pathol, 38, 1482, 10.1016/j.humpath.2007.02.013 Viacava, 2007, Markers of cell proliferation, apoptosis, and angiogenesis in thyroid adenomas: a comparative immunohistochemical and genetic investigation of functioning and nonfunctioning nodules, Thyroid, 17, 191, 10.1089/thy.2006.0175 Weinberger, 2007, Association of nuclear, cytoplasmic expression of galectin-3 with beta-catenin/Wnt-pathway activation in thyroid carcinoma, Arch Otolaryngol Head Neck Surg, 133, 503, 10.1001/archotol.133.5.503 Liu, 2008, Eur J Endocrinol, 158, 375, 10.1530/EJE-07-0492 Londero, 2007, Papillary microcarcinoma of the thyroid gland: is the immunohistochemical expression of cyclin D1 or galectin-3 in primary tumour an indicator of metastatic disease?, Acta Oncol, 1 Murphy, 2008, Identification of immunohistochemical biomarkers for papillary thyroid carcinoma using gene expression profiling, Hum Pathol, 39, 420, 10.1016/j.humpath.2007.07.015 Savin, 2008, Thyroid peroxidase and galectin-3 immunostaining in differentiated thyroid carcinoma with clinicopathologic correlation, Hum Pathol, 39, 1656, 10.1016/j.humpath.2008.04.006 Inohara, 2008, Cytoplasmic and serum galectin-3 in diagnosis of thyroid malignancies, Biochem Biophys Res Commun, 376, 605, 10.1016/j.bbrc.2008.09.041 Kashima, 1997, Cytoplasmic biotin-like activity interferes with immunohistochemical analysis of thyroid lesions: a comparison of antigen retrieval methods, Mod Pathol, 10, 515 Kim, 2002, The enhanced reactivity of endogenous biotin-like molecules by antigen retrieval procedures and signal amplification with tyramine, Histochem J, 34, 97, 10.1023/A:1020954611464 Bussolati, 1997, Retrieved endogenous biotin: a novel marker and a potential pitfall in diagnostic immunohistochemistry, Histopathology, 31, 400, 10.1046/j.1365-2559.1997.3020895.x Baloch, 2008, Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference, Diagn Cytopathol, 36, 425, 10.1002/dc.20830 Raphael, 2002, The meanings of markers: ancillary techniques in diagnosis of thyroid neoplasia, Endocr Pathol, 13, 301, 10.1385/EP:13:4:301 Carlson, 2006, HER2 testing in breast cancer: NCCN Task Force report and recommendations, J Natl Compr Canc Netw, 4, S1 Fowler, 2008, Application of immunohistochemistry to cytology, Arch Pathol Lab Med, 132, 373, 10.5858/2008-132-373-AOITC Carpi, 2007, Percutaneous large-needle aspiration biopsy histology of palpable thyroid nodules: technical and diagnostic performance, Histopathology, 51, 249, 10.1111/j.1365-2559.2007.02764.x Pazaitou-Panayiotou, 2007, Clinical features and therapeutic implication of papillary thyroid microcarcinoma, Thyroid, 17, 1085, 10.1089/thy.2007.0005 Noguchi, 2008, Papillary microcarcinoma, World J Surg, 32, 747, 10.1007/s00268-007-9453-0 Cvejic, 2005, Galectin-3 expression in papillary microcarcinoma of the thyroid, Histopathology, 47, 209, 10.1111/j.1365-2559.2005.02199.x Berho, 1995, Clear nuclear changes in Hashimoto's thyroiditis. A clinicopathologic study of 12 cases, Ann Clin Lab Sci, 25, 513 Prasad, 2004, Hashimoto's thyroiditis with papillary thyroid carcinoma (PTC)-like nuclear alterations express molecular markers of PTC, Histopathology, 45, 39, 10.1111/j.1365-2559.2004.01876.x Wiseman, 2007, Identification of molecular markers altered during transformation of differentiated into anaplastic thyroid carcinoma, Arch Surg, 142, 717, 10.1001/archsurg.142.8.717 Griffith, 2006, Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers, J Clin Oncol, 24, 5043, 10.1200/JCO.2006.06.7330 Finley, 2004, Discrimination of benign and malignant thyroid nodules by molecular profiling, Ann Surg, 240, 425, 10.1097/01.sla.0000137128.64978.bc Huang, 2001, Gene expression in papillary thyroid carcinoma reveals highly consistent profiles, Proc Natl Acad Sci USA, 98, 15044, 10.1073/pnas.251547398 Jarzab, 2005, Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications, Cancer Res, 65, 1587, 10.1158/0008-5472.CAN-04-3078 Finn, 2007, Expression microarray analysis of papillary thyroid carcinoma and benign thyroid tissue: emphasis on the follicular variant and potential markers of malignancy, Virchows Arch, 450, 249, 10.1007/s00428-006-0348-5 Lubitz, 2006, Microarray analysis of thyroid nodule fine-needle aspirates accurately classifies benign and malignant lesions, J Mol Diagn, 8, 490, 10.2353/jmoldx.2006.060080 Lubitz, 2005, Molecular analysis of minimally invasive follicular carcinomas by gene profiling, Surgery, 138, 1042, 10.1016/j.surg.2005.09.009 Martins, 2002, Galectin-3 messenger ribonucleic acid and protein are expressed in benign thyroid tumors, J Clin Endocrinol Metab, 87, 4806, 10.1210/jc.2002-020094 Bernet, 2002, Determination of galectin-3 messenger ribonucleic Acid overexpression in papillary thyroid cancer by quantitative reverse transcription-polymerase chain reaction, J Clin Endocrinol Metab, 87, 4792, 10.1210/jc.2002-020390 Takano, 2003, Ubiquitous expression of galectin-3 mRNA in benign and malignant thyroid tumors, Cancer Lett, 199, 69, 10.1016/S0304-3835(03)00343-4 Takano, 2005, Decreased relative expression level of trefoil factor 3 mRNA to galectin-3 mRNA distinguishes thyroid follicular carcinoma from adenoma, Cancer Lett, 219, 91, 10.1016/j.canlet.2004.07.004 Pagedar, 2008, Molecular classification of thyroid nodules by cytology, Laryngoscope, 118, 692, 10.1097/MLG.0b013e31815ed0ff Bojunga, 2004, Molecular detection of thyroid cancer: an update, Clin Endocrinol (Oxf), 61, 523, 10.1111/j.1365-2265.2004.02131.x Saussez, 2008, Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid disease, Thyroid, 18, 705, 10.1089/thy.2007.0361 Iurisci, 2009, Synthetic inhibitors of galectin-1 and -3 selectively modulate homotypic cell aggregation and tumor cell apoptosis, Anticancer Res, 29, 403 Bartolazzi, 2008, Thyroid cancer imaging in vivo by targeting the anti-apoptotic molecule galectin-3, PLoS One, 3, e3768, 10.1371/journal.pone.0003768