Skip to main content
SpringerLink
Log in

Thyroid Nodules

Cellular and Biochemical Markers for Malignancy

  • Chapter
Thyroid Cancer

  • 1506 Accesses

Abstract

Although the majority of histologic specimens obtained by fine-needle aspiration (FNA) yield a definitive diagnosis, 10–30% are deemed indeterminate. Generally, surgery is recommended for these patients, as up to one quarter of these nodules are found to be malignant. Notwithstanding that concern, 75% of patients with a benign nodule undergo an unnecessary procedure. In an effort to reduce these potentially avoidable surgeries, a number of biochemical and molecular markers have been developed to assist in the discernment of benign from malignant nodules.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 269.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 339.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Xu XC, el-Naggar AK, Lotan R. Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications. Am J Pathol 1995; 147:815–822.

    PubMed  CAS  Google Scholar 

  2. Coli A, Bigotti G, Zucchetti F, et al. Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia. Histopathology 2002; 40:80–87.

    PubMed  CAS  Google Scholar 

  3. Cvejic D, Savin S, Paunovic I, et al. Immunohistochemical localization of galectin-3 in malignant and benign human thyroid tissue. Anticancer Res 1998; 18:2637–2641.

    PubMed  CAS  Google Scholar 

  4. Martins L, Matsuo SE, Ebina KN, et al. Galectin-3 messenger ribonucleic acid and protein are expressed in benign thyroid tumors. J Clin Endocrinol Metab 2002; 87:4806–4810.

    PubMed  CAS  Google Scholar 

  5. Fernandez PL, Merino MJ, Gomez M, et al. Galectin-3 and laminin expression in neoplastic and non-neoplastic thyroid tissue. J Pathol 1997; 181:80–86.

    PubMed  CAS  Google Scholar 

  6. Herrmann ME, LiVolsi VA, Pasha TL, et al. Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions. Arch Pathol Lab Med 2002; 126:710–713.

    PubMed  CAS  Google Scholar 

  7. Nucera C, Mazzon E, Cailou B, et al. Human galectin-3 immunoexpression in thyroid follicular adenomas with cell atypia. J Endocrinol Invest 2005; 28:106–112.

    PubMed  CAS  Google Scholar 

  8. Papotti M, Rodgriguez J, DePompa R, Bartolazzi A, Rosai J. Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Mod Pathol 2005; 18:541–546.

    PubMed  CAS  Google Scholar 

  9. Oestreicher-Kedem Y, Halpern M, Roizman P, et al. Diagnostic value of galectin-3 as a marker for malignancy in follicular patterned thyroid lesions. Head & Neck 2004; 26:960–966.

    Google Scholar 

  10. Orlandi F, Saggiorato E, Pivano G, et al. Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer Res 1998; 58:3015–3020.

    PubMed  CAS  Google Scholar 

  11. Aratake Y, Umeki K, Kiyoyama K, et al. Diagnostic utility of galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules. Diagn Cytopathol 2002; 26:366–372.

    PubMed  Google Scholar 

  12. Gasbarri A, Martegani MP, Del Prete F, et al. Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules. J Clin Oncol 1999; 17:3494–3502.

    PubMed  CAS  Google Scholar 

  13. Bartolazzi A, Gasbarri A, Papotti M, et al. Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 2001; 357:1644–1650.

    PubMed  CAS  Google Scholar 

  14. Saggiorato E, Cappia S, De Giuli P, et al. Galectin-3 as a presurgical immunocytodiagnostic marker of minimally invasive follicular thyroid carcinoma. J Clin Endocrinol Metab 2001; 86:5152–5158.

    PubMed  CAS  Google Scholar 

  15. Papotti M, Volante M, Saggiorato E, et al. Role of galectin-3 immunodetection in the cytological diagnosis of thyroid cystic papillary carcinoma. Eur J Endocrinol 2002; 147:515–521.

    PubMed  CAS  Google Scholar 

  16. Giannini R, Faviana P, Cavinato T, et al. 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 2003; 13:765–770.

    PubMed  CAS  Google Scholar 

  17. Bernet VJ, Anderson J, Vaishnav Y, et al. Determination of galectin-3 messenger ribonucleic Acid overexpression in papillary thyroid cancer by quantitative reverse transcription-polymerase chain reaction. J Clin Endocrinol Metab 2002; 87:4792–4796.

    PubMed  CAS  Google Scholar 

  18. Niedziela M, Maceluch J, Korman E. Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in children and adolescents. J Clin Endocrinol Metab 2002; 87:4411–4415.

    PubMed  CAS  Google Scholar 

  19. Shay JW. Telomerase in cancer: diagnostic, prognostic, and therapeutic implications. Cancer J Sci Am 1998; 4(Suppl 1):S26–S34.

    PubMed  Google Scholar 

  20. Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266:2011–2015.

    PubMed  CAS  Google Scholar 

  21. Haugen BR, Nawaz S, Markham N, et al. Telomerase activity in benign and malignant thyroid tumors. Thyroid 1997; 7:337–342.

    PubMed  CAS  Google Scholar 

  22. Umbricht CB, Saji M, Westra WH, et al. Telomerase activity: a marker to distinguish follicular thyroid adenoma from carcinoma. Cancer Res 1997; 57:2144–2147.

    PubMed  CAS  Google Scholar 

  23. Yashima K, Vuitch F, Gazdar AF, Fahey TJ III. Telomerase activity in benign and malignant thyroid diseases. Surgery 1997; 122:1141–1145; discussion 1145–1146.

    PubMed  CAS  Google Scholar 

  24. Matthews P, Jones CJ, Skinner J, et al. Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications. J Pathol 2001; 194:183–193.

    PubMed  CAS  Google Scholar 

  25. Saji M, Westra WH, Chen H, et al. Telomerase activity in the differential diagnosis of papillary carcinoma of the thyroid. Surgery 1997; 122:1137–1140.

    PubMed  CAS  Google Scholar 

  26. Aogi K, Kitahara K, Buley I, et al. Telomerase activity in lesions of the thyroid: application to diagnosis of clinical samples including fine-needle aspirates. Clin Cancer Res 1998; 4:1965–1970.

    PubMed  CAS  Google Scholar 

  27. Ito Y, Yoshida H, Tomoda C, et al. Telomerase activity in thyroid neoplasms evaluated by the expression of human telomerase reverse transcriptase (hTERT). Anticancer Res 2005; 25:509–514.

    PubMed  CAS  Google Scholar 

  28. Saji M, Xydas S, Westra WH, et al. Human telomerase reverse transcriptase (hTERT) gene expression in thyroid neoplasms. Clin Cancer Res 1999; 5:1483–1489.

    PubMed  CAS  Google Scholar 

  29. Zeiger MA, Smallridge RC, Clark DP, et al. Human telomerase reverse transcriptase (hTERT) gene expression in FNA samples from thyroid neoplasms. Surgery 1999; 126:1195–1198; discussion 1198–1199.

    PubMed  CAS  Google Scholar 

  30. Aogi K, Kitahara K, Urquidi V, et al. Comparison of telomerase and CD44 expression as diagnostic tumor markers in lesions of the thyroid. Clin Cancer Res 1999; 5:2790–2797.

    PubMed  CAS  Google Scholar 

  31. Siddiqui MT, Greene KL, Clark DP, et al. Human telomerase reverse transcriptase expression in Diff-Quik-stained FNA samples from thyroid nodules. Diagn Mol Pathol 2001; 10:123–129.

    PubMed  CAS  Google Scholar 

  32. Liou MJ, Chan EC, Lin JD, Liu FH, Chao TC. Human telomerase reverse transcriptase (hTERT) gene expression in FNA samples from thyroid neoplasms. Cancer Lett 2003; 191:223–227.

    PubMed  CAS  Google Scholar 

  33. Kammori M, Nakamura K, Hashimoto M, et al. Clinical application of human telomerase reverse transcriptase gene expression in thyroid follicular tumors by fine-needle aspirations using in situ hybridization. Int J Oncol 2003; 22:985–991.

    PubMed  CAS  Google Scholar 

  34. De Micco C, Zoro P, Garcia S, et al. Thyroid peroxidase immunodetection as a tool to assist diagnosis of thyroid nodules on fine-needle aspiration biopsy. Eur J Endocrinol 1994; 131:474–479.

    PubMed  Google Scholar 

  35. De Micco C, Vasko V, Garcia S, et al. Fine-needle aspiration of thyroid follicular neoplasm: diagnostic use of thyroid peroxidase immunocytochemistry with monoclonal antibody 47. Surgery 1994; 116:1031–1035.

    PubMed  Google Scholar 

  36. De Micco C, Vassko V, Henry JF. The value of thyroid peroxidase immunohistochemistry for preoperative fine-needle aspiration diagnosis of the follicular variant of papillary thyroid cancer. Surgery 1999; 126:1200–1204.

    PubMed  Google Scholar 

  37. Henry JF, Denizot A, Porcelli A, et al. Thyroperoxidase immunodetection for the diagnosis of malignancy on fine-needle aspiration of thyroid nodules. World J Surg 1994; 18:529–534.

    PubMed  CAS  Google Scholar 

  38. Garcia S, Vassko V, Henry JF, De Micco C. Comparison of thyroid peroxidase expression with cellular proliferation in thyroid follicular tumors. Thyroid 1998; 8:745–749.

    PubMed  CAS  Google Scholar 

  39. Christensen L, Blichert-Toft M, Brandt M, et al. Thyroperoxidase (TPO) immunostaining of the solitary cold thyroid nodule. Clin Endocrinol 2000; 53:161–169.

    CAS  Google Scholar 

  40. Pluot M, Faroux MJ, Flament JB, Patey M, Theobald S, Delisle MJ. Quantitative cytology and thyroperoxidase immunochemistry: new tools in evaluating thyroid nodules by fine-needle aspiration. Cancer Detect Prev 1996; 20:285–293.

    PubMed  CAS  Google Scholar 

  41. Faroux MJ, Theobald S, Pluot M, et al. Evaluation of the monoclonal antibody antithyroperoxidase MoAb47 in the diagnostic decision of cold thyroid nodules by fine-needle aspiration. Pathol Res Pract 1997; 193:705–712.

    PubMed  CAS  Google Scholar 

  42. Lazar V, Bidart JM, Caillou B, et al. Expression of the Na+/I-symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. J Clin Endocrinol Metab 1999; 84:3228–3234.

    PubMed  CAS  Google Scholar 

  43. Tanaka T, Umeki K, Yamamoto I, et al. Immunohistochemical loss of thyroid peroxidase in papillary thyroid carcinoma: strong suppression of peroxidase gene expression. J Pathol 1996; 179:89–94.

    PubMed  CAS  Google Scholar 

  44. Herschman HR. Prostaglandin synthase 2. Biochim Biophys Acta 1996; 1299:125–140.

    PubMed  Google Scholar 

  45. Specht MC, Tucker ON, Hocever M, et al. Cyclooxygenase-2 expression in thyroid nodules. J Clin Endocrinol Metab 2002; 87:358–363.

    PubMed  CAS  Google Scholar 

  46. Lo CY, Lam KY, Leung PP, Luk JM. High prevalence of cyclooxy-genase 2 expression in papillary thyroid carcinoma. Eur J Endocrinol 2005; 152:545–550.

    PubMed  CAS  Google Scholar 

  47. Sato H, Ino Y, Miura A, et al. Dysadherin: expression and clinical significance in thyroid carcinoma. J Clin Endocrinol Metab 2003; 88:4407–4412.

    PubMed  CAS  Google Scholar 

  48. Smyth P, Sheils O, Finn S, et al. Real-time quantitative analysis of E-cadherin expression in ret/PTC-1-activated thyroid neoplasms. Int J Surg Pathol 2001; 9:265–272.

    PubMed  CAS  Google Scholar 

  49. Ermak G, Gerasimov G, Troshina K, et al. Deregulated alternative splicing of CD44 messenger RNA transcripts in neoplastic and nonneoplastic lesions of the human thyroid. Cancer Res 1995; 55:4594–4598.

    PubMed  CAS  Google Scholar 

  50. Ermak G, Jennings T, Robinson L, et al. Restricted patterns of CD44 variant exon expression in human papillary thyroid carcinoma. Cancer Res 1996; 56:1037–1042.

    PubMed  CAS  Google Scholar 

  51. Kim JY, Cho H, Rhee BD, Kim HY. Expression of CD44 and cyclin D1 in fine needle aspiration cytology of papillary thyroid carcinoma. Acta Cytol 2002; 46:679–683.

    PubMed  Google Scholar 

  52. Takano T, Sumizaki H, Amino N. Detection of CD44 variants in fine needle aspiration biopsies of thyroid tumor by RT-PCR. J Exp Clin Cancer Res 1997; 16:267–271.

    PubMed  CAS  Google Scholar 

  53. Takano T, Matsuzuka F, Miyauchi A, et al. Restricted expression of oncofetal fibronectin mRNA in thyroid papillary and anaplastic carcinoma: an in situ hybridization study. Br J Cancer 1998; 78:221–224.

    PubMed  CAS  Google Scholar 

  54. Higashiyama T, Takano T, Matsuzuka F, et al. Measurement of the expression of oncofetal fibronectin mRNA in thyroid carcinomas by competitive reverse transcription-polymerase chain reaction. Thyroid 1999; 9:235–240.

    PubMed  CAS  Google Scholar 

  55. Takano T, Matsuzuka F, Sumizaki H, et al. Rapid detection of specific messenger RNAs in thyroid carcinomas by reverse transcription-PCR with degenerate primers: specific expression of oncofetal fibronectin messenger RNA in papillary carcinoma. Cancer Res 1997; 57:3792–3797.

    PubMed  CAS  Google Scholar 

  56. Takano T, Miyauchi A, Yokozawa T, et al. Accurate and objective preoperative diagnosis of thyroid papillary carcinomas by reverse transcription-PCR detection of oncofetal fibronectin messenger RNA in fine-needle aspiration biopsies. Cancer Res 1998; 58:4913–4917.

    PubMed  CAS  Google Scholar 

  57. Takano T, Miyauchi A, Yokozawa T, et al. Preoperative diagnosis of thyroid papillary and anaplastic carcinomas by real-time quantitative reverse transcription-polymerase chain reaction of oncofetal fibronectin messenger RNA. Cancer Res 1999; 59:4542–4545.

    PubMed  CAS  Google Scholar 

  58. Aust G, Eichler W, Laue S, et al. CD97: a dedifferentiation marker in human thyroid carcinomas. Cancer Res 1997; 57:1798–1806.

    PubMed  CAS  Google Scholar 

  59. Cheung CC, Ezzat S, Freeman JL, et al. Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol 2001; 14:338–342.

    PubMed  CAS  Google Scholar 

  60. Sugg SL, Ezzat S, Rosen IB, et al. Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab 1998; 83:4116–4122.

    PubMed  CAS  Google Scholar 

  61. Elisei R, Romei C, Vorontsova T, et al. RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults. J Clin Endocrinol Metab 2001; 86:3211–3216.

    PubMed  CAS  Google Scholar 

  62. Fusco A, Chiappetta G, Hui P, et al. Assessment of RET/PTC oncogene activation and clonality in thyroid nodules with incomplete morphological evidence of papillary carcinoma: a search for the early precursors of papillary cancer. Am J Pathol 2002; 160:2157–2167.

    PubMed  CAS  Google Scholar 

  63. Cheung CC, Carydis B, Ezzat S, et al. Analysis of ret/PTC gene rearrangements refines the fine needle aspiration diagnosis of thyroid cancer. J Clin Endocrinol Metab 2001; 86:2187–2190.

    PubMed  CAS  Google Scholar 

  64. Miettinen M, Karkkainen P. Differential reactivity of HBME-1 and CD15 antibodies in benign and malignant thyroid tumours. Preferential reactivity with malignant tumours. Virchows Arch 1996; 429:213–219.

    PubMed  CAS  Google Scholar 

  65. Mase T, Funahashi H, Koshikawa T, et al. HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm. Endocr J 2003; 50:173–177.

    PubMed  Google Scholar 

  66. van Hoeven KH, Kovatich AJ, Miettinen M. Immunocytochemical evaluation of HBME-1, CA 19-9, and CD-15 (Leu-M1) in fine-needle aspirates of thyroid nodules. Diagn Cytopathol 1998; 18:93–97.

    PubMed  Google Scholar 

  67. Sack MJ, Astengo-Osuna C, Lin BT, et al. HBME-1 immunostaining in thyroid fine-needle aspirations: a useful marker in the diagnosis of carcinoma. Mod Pathol 1997; 10:668–674.

    PubMed  CAS  Google Scholar 

  68. Ito Y, Yoshida H, Tomoda C, et al. HBME-1 expression in follicular tumor of the thyroid: an investigation of whether it can be used as a marker to diagnose follicular carcinoma. Anticancer Res 2005; 25:179–182.

    PubMed  CAS  Google Scholar 

  69. Chiappetta G, Bandiera A, Berlingieri MT, et al. The expression of the high mobility group HMGI (Y) proteins correlates with the malignant phenotype of human thyroid neoplasias. Oncogene 1995; 10:1307–1314.

    PubMed  CAS  Google Scholar 

  70. Chiappetta G, Tallini G, De Biasio MC, et al. Detection of high mobility group I HMGI(Y) protein in the diagnosis of thyroid tumors: HMGI(Y) expression represents a potential diagnostic indicator of carcinoma. Cancer Res 1998; 58:4193–4198.

    PubMed  CAS  Google Scholar 

  71. Kimura ET, Nikiforova MN, Zhu Z, et al. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 2003; 63:1454–1457.

    PubMed  CAS  Google Scholar 

  72. Cohen Y, Xing M, Mambo E, et al. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst 2003; 95:625–627.

    PubMed  CAS  Google Scholar 

  73. Xu X, Quiros RM, Gattuso P, et al. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res 2003; 63:4561–4567.

    PubMed  CAS  Google Scholar 

  74. Cohen Y, Rosenbaum E, Clark DP, et al. Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules. Clin Cancer Res 2004; 10:2761–2765.

    PubMed  CAS  Google Scholar 

  75. Xing M, Tufano RP, Tufaro AP, et al. Detection of BRAF mutation on fine needle aspiration biopsy specimens: a new diagnostic tool for papillary thyroid cancer. J Clin Endocrinol Metab 2004; 89:2867–2872.

    PubMed  CAS  Google Scholar 

  76. Hayashida N, Namba H, Kumagai A, et al. A rapid and simple detection method for the BRAF (T1796A) mutation in fine-needle aspirated thyroid carcinoma cells. Thyroid 2004; 14:910–915.

    PubMed  CAS  Google Scholar 

  77. Pinkus GS, Kurtin PJ. Epithelial membrane antigen—a diagnostic discriminant in surgical pathology: immunohistochemical profile in epithelial, mesenchymal, and hematopoietic neoplasms using paraffin sections and monoclonal antibodies. Hum Pathol 1985; 16:929–940.

    PubMed  CAS  Google Scholar 

  78. Damiani S, Fratamico F, Lapertosa G, et al. Alcian blue and epithelial membrane antigen are useful markers in differentiating benign from malignant papillae in thyroid lesions. Virchows Arch A Pathol Anat Histopathol 1991; 419:131–135.

    PubMed  CAS  Google Scholar 

  79. Wilson NW, Pambakian H, Richardson TC, et al. Epithelial markers in thyroid carcinoma: an immunoperoxidase study. Histopathology 1986; 10:815–829.

    PubMed  CAS  Google Scholar 

  80. Mitselou A, Vougiouklakis TG, Peschos D, et al. Immunohistochemical study of the expression of S-100 protein, epithelial membrane antigen, cytokeratin and carcinoembryonic antigen in thyroid lesions. Anticancer Res 2002; 22:1777–1780.

    PubMed  CAS  Google Scholar 

  81. Cheifetz RE, Davis NL, Robinson BW, et al. Differentiation of thyroid neoplasms by evaluating epithelial membrane antigen, Leu-7 antigen, epidermal growth factor receptor, and DNA content. Am J Surg 1994; 167:531–534.

    PubMed  CAS  Google Scholar 

  82. Ghali VS, Jimenez EJ, Garcia RL. Distribution of Leu-7 antigen (HNK-1) in thyroid tumors: its usefulness as a diagnostic marker for follicular and papillary carcinomas. Hum Pathol 1992; 23:21–25.

    PubMed  CAS  Google Scholar 

  83. Khan A, Baker SP, Patwardhan NA, Pullman JM. CD57 (Leu-7) expression is helpful in diagnosis of the follicular variant of papillary thyroid carcinoma. Virchows Arch 1998; 432:427–432.

    PubMed  CAS  Google Scholar 

  84. Ostrowski ML, Brown RW, Wheeler TM, et al. Leu-7 immunoreactivity in cytologic specimens of thyroid lesions, with emphasis on follicular neoplasms. Diagn Cytopathol 1995; 12:297–302.

    PubMed  CAS  Google Scholar 

  85. Suh N, Wang Y, Williams CR, et al. A new ligand for the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), GW7845, inhibits rat mammary carcinogenesis. Cancer Res 1999; 59:5671–5673.

    PubMed  CAS  Google Scholar 

  86. Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science 2000; 289:1357–1360.

    PubMed  CAS  Google Scholar 

  87. Nikiforova MN, Biddinger PW, Caudill CM, et al. PAX8-PPARgamma rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses. Am J Surg Pathol 2002; 26:1016–1023.

    PubMed  Google Scholar 

  88. Nikiforova MN, Lynch RA, Biddinger PW, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab 2003; 88:2318–2326.

    PubMed  CAS  Google Scholar 

  89. Marques AR, Espadinha C, Catarino AL, et al. Expression of PAX8-PPARgamma1 Rearrangements in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab 2002; 87:3947–3952.

    PubMed  CAS  Google Scholar 

  90. Dwight T, Thoppe SR, Foukakis T, et al. Involvement of the PAX8/peroxisome proliferator-activated receptor gamma rearrangement in follicular thyroid tumors. J Clin Endocrinol Metab 2003; 88:4440–4445.

    PubMed  CAS  Google Scholar 

  91. Cheung L, Messina M, Gill A, et al. Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab 2003; 88:354–357.

    PubMed  CAS  Google Scholar 

  92. Arai T, Watanabe M, Onodera M, et al. Reduced nm 23-H1 messenger RNA expression in metastatic lymph nodes from patients with papillary carcinoma of the thyroid. Am J Pathol 1993; 142:1938–1944.

    PubMed  CAS  Google Scholar 

  93. Arai T, Yamashita T, Urano T, et al. Preferential reduction of nm23-H1 gene product in metastatic tissues from papillary and follicular carcinomas of the thyroid. Mod Pathol 1995; 8:252–256.

    PubMed  CAS  Google Scholar 

  94. Okubo T, Inokuma S, Takeda S, Itoyama S, Kinoshita K, Sugawara I. Expression of nm23-H1 gene product in thyroid, ovary, and breast cancers. Cell Biophys 1995; 26:205–213.

    PubMed  CAS  Google Scholar 

  95. Zou M, Shi Y, al-Sedairy S, Farid NR. High levels of Nm23 gene expression in advanced stage of thyroid carcinomas. Br J Cancer 1993; 68:385–388.

    PubMed  CAS  Google Scholar 

  96. Zafon C, Obiols G, Castellvi J, et al. nm23-H1 immunoreactivity as a prognostic factor in differentiated thyroid carcinoma. J Clin Endocrinol Metab 2001; 86:3975–3980.

    PubMed  CAS  Google Scholar 

  97. Farley DR, Eberhardt NL, Grant CS, et al. Expression of a potential metastasis suppressor gene (nm23) in thyroid neoplasms. World J Surg 1993; 17:615–20; discussion 620–621.

    PubMed  CAS  Google Scholar 

  98. Bertheau P, De La Rosa A, Steeg PS, Merino MJ. NM23 protein in neoplastic and nonneoplastic thyroid tissues. Am J Pathol 1994; 145:26–32.

    PubMed  CAS  Google Scholar 

  99. Luo W, Matsuo K, Nagayama Y, et al. Immunohistochemical analysis of expression of nm23-H1/nucleoside diphosphate kinase in human thyroid carcinomas: lack of correlation between its expression and lymph node metastasis. Thyroid 1993; 3:105–109.

    PubMed  CAS  Google Scholar 

  100. Trovato M, Villari D, Ruggeri RM, et al. Expression of CD30 ligand and CD30 receptor in normal thyroid and benign and malignant thyroid nodules. Thyroid 2001; 11:621–628.

    PubMed  CAS  Google Scholar 

  101. Sorrentino R, Libertini S, Pallante PL, et al. Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. J Clin Endocrinol Metab 2005; 90:928–935.

    PubMed  CAS  Google Scholar 

  102. Nikiforov YE. Editorial: Anaplastic carcinoma of the thyroid—Will Aurora B light a path for treatment? J Clin Endocrinol Metab 2005; 90:1243–1245.

    PubMed  CAS  Google Scholar 

  103. Tuccari G, Barresi G. Immunohistochemical demonstration of ceruloplasmin in follicular adenomas and thyroid carcinomas. Histopathology 1987; 11:723–731.

    PubMed  CAS  Google Scholar 

  104. Kondi-Pafiti A, Smyrniotis V, Frangou M, et al. Immunohistochemical study of ceruloplasmin, lactoferrin and secretory component expression in neoplastic and non-neoplastic thyroid gland diseases. Acta Oncol 2000; 39:753–756.

    PubMed  CAS  Google Scholar 

  105. de Camargo R, Longatto Filho A, Alves VA, et al. Lactoferrin in thyroid lesions: immunoreactivity in fine needle aspiration biopsy samples. Acta Cytol 1996; 40:408–413.

    Google Scholar 

  106. Stoker M, Gherardi E, Perryman M, Gray J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature 1987; 327:239–242.

    PubMed  CAS  Google Scholar 

  107. Di Renzo MF, Olivero M, Ferro S, et al. Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 1992; 7:2549–2553.

    PubMed  Google Scholar 

  108. Belfiore A, Gangemi P, Costantino A, et al. Negative/low expression of the Met/hepatocyte growth factor receptor identifies papillary thyroid carcinomas with high risk of distant metastases. J Clin Endocrinol Metab 1997; 82:2322–2328.

    PubMed  CAS  Google Scholar 

  109. Ippolito A, Vella V, La Rosa GL, et al. Immunostaining for Met/HGF receptor may be useful to identify malignancies in thyroid lesions classified suspicious at fine-needle aspiration biopsy. Thyroid 2001; 11:783–787.

    PubMed  CAS  Google Scholar 

  110. Xing M, Usadel H, Cohen Y, et al. Methylation of the thyroidstimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing. Cancer Res 2003; 63:2316–2321.

    PubMed  CAS  Google Scholar 

  111. Erkilic S, Aydin A, Kocer NE. Diagnostic utility of cytokeratin 19 expression in multinodular goiter with papillary areas and papillary carcinoma of thyroid. Endocr Pathol 2002; 13:207–211.

    PubMed  CAS  Google Scholar 

  112. Raphael SJ, McKeown-Eyssen G, Asa SL. High-molecular-weight cytokeratin and cytokeratin-19 in the diagnosis of thyroid tumors. Mod Pathol 1994; 7:295–300.

    PubMed  CAS  Google Scholar 

  113. Beesley MF, McLaren KM. Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules. Histopathology 2002; 41:236–243.

    PubMed  CAS  Google Scholar 

  114. Hirokawa M, Inagaki A, Kobayashi H, et al. Expression of cytokeratin 19 in cytologic specimens of thyroid. Diagn Cytopathol 2000; 22:197–198.

    PubMed  CAS  Google Scholar 

  115. Nasser SM, Pitman MB, Pilch BZ, Faquin WC. Fine-needle aspiration biopsy of papillary thyroid carcinoma: diagnostic utility of cytokeratin 19 immunostaining. Cancer 2000; 90:307–311.

    PubMed  CAS  Google Scholar 

  116. Finley DJ, Lubitz CC, Wei C, Zhu B, Fahey TJ III. Advancing the molecular diagnosis of thyroid nodules: Defining benign lesions by molecular profiling. Thyroid 2005; 15:562–568.

    PubMed  CAS  Google Scholar 

  117. Weber F, Shen L, Aldred MA, et al. Genetic classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination. J Clin Endocrinol Metab 2005; 90:2512–2521.

    PubMed  CAS  Google Scholar 

  118. Chevillard S, Ugolin N, Vielh P, et al. Gene expression profiling of differentiate thyroid neoplasms: diagnostic and clinical implications. Clin Cancer Res 2004; 10:6586–6597.

    PubMed  CAS  Google Scholar 

  119. Barden CB, Shister KW, Zhu B, et al. Classification of follicular thyroid tumors by molecular signature: results of gene profiling. Clin Cancer Res 2003; 9:1792–1800.

    PubMed  CAS  Google Scholar 

  120. Finley DJ, Arora N, Zhu B, et al. Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules. J Clin Endocrinol Metab 2004; 89:3214–3223.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Endocrinology, Department of Medicine, Washington Hospital Center, Washington, DC

    Kathleen A. Prendergast MD (Attending Physician)

Authors
  1. Kathleen A. Prendergast MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Washington Hospital Center, Washington, DC

    Leonard Wartofsky MD, MPH, MACP  & Douglas Van Nostrand MD, FACP, FACNP  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Prendergast, K.A. (2006). Thyroid Nodules. In: Wartofsky, L., Van Nostrand, D. (eds) Thyroid Cancer. Humana Press. https://doi.org/10.1007/978-1-59259-995-0_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-995-0_19

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-462-3

  • Online ISBN: 978-1-59259-995-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation