Thyroid Cancer: Identification of Gene Expression Markers for Diagnosis

  • Obi L. Griffith
  • Adrienne Melck
  • Steven J. M. Jones
  • Sam M. Wiseman
Part of the Methods of Cancer Diagnosis, Therapy and Prognosis book series (HAYAT, volume 7)


The human genome contains tens of thousands of gene loci which code for an even greater number of different protein and RNA products. The highly complex temporal and spatial expression of these genes makes possible all the biological processes of life from development and differentiation to homeostasis, aging, and programmed cell death. Therefore, it is not surprising that altered gene expression by mutation or deregulation is fundamental for the development of many human diseases including cancer. In some cases, cancers can be linked to large changes such as deletions or duplications of entire gene(s). In other cases, more subtle changes in expression levels of larger numbers of genes are involved. Until recently, cancer diagnosis was dependent on pathological methods and imaging studies that often require a tumor of significant size and suffer from poor sensitivity (Ahmed 2002). The recent development of gene expression profiling tools, promises to identify new and improved diagnostic tools at the molecular level.


Thyroid Cancer Fine Needle Aspiration Biopsy Massively Parallel Signature Sequencing Follicular Neoplasm Nodular Thyroid Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Ahmed FE (2002) Molecular techniques for studying gene expression in carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 20:77-116PubMedCrossRefGoogle Scholar
  2. Ahmed FE (2006) Microarray RNA transcriptional profiling: Part II. Analytical considerations and annotation. Expert Rev Mol Diagn 6:703-715PubMedCrossRefGoogle Scholar
  3. Aldred MA, Huang Y, Liyanarachchi S, Pellegata NS, Gimm O, Jhiang S, Davuluri RV, de La Chapelle A, Charis E (2004) Papillary and follicular thyroid carcinomas show distinctly different microarray expression profiles and can be distinguished by a minimum of five genes. J Clin Oncol 22:3531-3539PubMedCrossRefGoogle Scholar
  4. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503-511PubMedCrossRefGoogle Scholar
  5. Arnaldi LAT, Borra RC, Maciel RMB, Cerutti JM (2005) Gene expression profiles reveal that DCN, DIO1, and DIO2 are underexpressed in benign and malignant thyroid tumors. Thyroid 15:210-221PubMedCrossRefGoogle Scholar
  6. Audic S, Claverie JM (1997) The significance of digital gene expression profiles. Genome Res 7:986-995PubMedGoogle Scholar
  7. Bainbridge MN, Warren RL, Hirst M, Romanuik T, Zeng T, Go A, Delaney A, Griffith M, Hickenbotham M, Magrini V, Mardis ER, Sadar MD, Siddiqui AS, Marra MA, Jones SJ (2006) Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics 7:246PubMedCrossRefGoogle Scholar
  8. Baloch ZW, LiVolsi VA (2002) Intraoperative assessment of thyroid and parathyroid lesions. Semin Diagn Pathol 19:219-226PubMedGoogle Scholar
  9. Barden CB, Shister KW, Zhu B, Guiter G, Greenblatt DY, Zeiger MA, Fahey TJ III (2003) Classification of follicular thyroid tumors by molecular signature: results of gene profiling. Clin Cancer Res 9:1792-1800PubMedGoogle Scholar
  10. Barroeta JE, Baloch ZW, Lal P, Pasha TL, Zhang PJ, LiVolsi VA (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 17:225-234PubMedCrossRefGoogle Scholar
  11. Bartolazzi A, Gasbarri A, Papotti M, Bussolati G, Lucante T, Khan A, Inohara H, Marandino F, Orlandi F, Nardi F, Vecchione A, Tecce R, Larsson O (2001) Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644-1650PubMedCrossRefGoogle Scholar
  12. Belfiore A, Gangemi P, Costantino A, Russo G, Santonocito GM, Ippolito O, Di Renzo MF, Comoglio P, Fiumara A, Vigneri R (1997) Negative/low expression of the Met/hepatocyte growth factor receptor identifies papillary thyroid carcinomas with high risk of distant metastases. J Clin Endocrinol Metab 82:2322-2328PubMedCrossRefGoogle Scholar
  13. Bentley DR (2006) Whole-genome re-sequencing. Curr Opin Genet Dev 16:545-552PubMedCrossRefGoogle Scholar
  14. Bergstrom JD, Westermark B, Heldin NE (2000) Epidermal growth factor receptor signaling activates met in human anaplastic thyroid carcinoma cells. Exp Cell Res 259:293-299PubMedCrossRefGoogle Scholar
  15. Caraway NP, Sneige N, Samaan NA (1993) Diagnostic pitfalls in thyroid fine-needle aspiration: a review of 394 cases. Diagn Cytopathol 9:345-350PubMedCrossRefGoogle Scholar
  16. Cerutti JM, Delcelo R, Amadei MJ, Nakabashi C, Maciel RMB, Peterson B, Shoemaker J, Riggins GJ (2004) A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression. J Clin Invest 113:1234-1242PubMedGoogle Scholar
  17. Chen KT, Lin JD, Chao TC, Hsueh C, Chang CA, Weng HF, Chan ER (2001) Identifying differentially expressed genes associated with metastasis of follicular thyroid cancer by cDNA expression array. Thyroid 11:41-46PubMedCrossRefGoogle Scholar
  18. Chevillard S, Ugolin N, Vielh P, Ory K, Levalois C, Elliott D, Clayman GL, El-Naggar AK (2004) Gene expression profiling of differentiated thyroid neoplasms. Clin Cancer Res 10:6586-6597PubMedCrossRefGoogle Scholar
  19. Choi YL, Kim MK, Suh JW, Han J, Kim JH, Yang JH, Nam SJ (2005) Immunoexpression of HBME-1, high molecular weight cytokeratin, cytokeratin 19, thyroid transcription factor-1, and E-cadherin in thyroid carcinomas. J Korean Med Sci 20:853-859PubMedCrossRefGoogle Scholar
  20. Collet JF, Hurbain I, Prengel C, Utzmann O, Scetbon F, Bernaudin JF, Fajac A (2005) Galectin-3 immunodetection in follicular thyroid neoplasms: a prospective study on fine-needle aspiration samples. Br J Cancer 93:1175-1181PubMedCrossRefGoogle Scholar
  21. Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 295:2164-2167PubMedCrossRefGoogle Scholar
  22. Di Renzo MF, Olivero M, Ferro S, Prat M, Bongarzone I, Pilotti S, Belfiore A, Costantino A, Vigneri R, Pierotti MA, Comoglio P (1992) Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 7:2549-2553PubMedGoogle Scholar
  23. Eszlinger M, Krohn K, Paschke R (2001) Complementary DNA expression array analysis suggests a lower expression of signal transduction proteins and receptors in cold and hot thyroid nodules. J Clin Endocrinol Metab 86:4834-4842PubMedCrossRefGoogle Scholar
  24. Finley DJ, Arora N, Zhu B, Gallagher L, Fahey TJIII (2004a) Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules. J Clin Endocrinol Metab 89:3214-3223PubMedCrossRefGoogle Scholar
  25. Finley DJ, Zhu B, Barden CB, Fahey TJ III (2004b) Discrimination of benign and malignant thyroid nodules by molecular profiling. Ann Surg 240:425-436PubMedCrossRefGoogle Scholar
  26. Finn SP, Smyth P, Cahill S, Streck C, O’Regan EM, Flavin R, Sherlock J, Howells D, Henfrey R, Cullen M, Toner M, Timon C, O’Leary JJ, Sheils OM (2007) Expression microarray analysis of papillary thyroid carcinoma and benign thyroid tissue: emphasis on the follicular variant and potential markers of malignancy. Virchows Archive 450:249-260CrossRefGoogle Scholar
  27. Franc B, de la Salmoniere P, Lange F, Hoang C, Louvel A, de Roquancourt A, Vilde F, Hejblum G, Chevret S, Chastang C (2003) Interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma. Hum Pathol 34:1092-1100PubMedCrossRefGoogle Scholar
  28. Fu LM, Fu-Liu CS (2004) Multi-class cancer subtype classification based on gene expression signatures with reliability analysis. FEBS Lett 561:186-190PubMedCrossRefGoogle Scholar
  29. Gharib H, Goellner JR (1993) Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med 118:282-289PubMedGoogle Scholar
  30. Ginestier C, Charafe-Jauffret E, Bertucci F, Eisinger F, Geneix J, Bechlian D, Conte N, Adelaide J, Toiron Y, Nguyen C, Viens P, Mozziconacci MJ, Houlgatte R, Birnbaum D, Jacquemier J (2002) Distinct and complementary information provided by use of tissue and DNA microarrays in the study of breast tumor markers. Am J Pathol 161:1223-1233PubMedCrossRefGoogle Scholar
  31. Giordano TJ, Kuick R, Thomas DG, Misek DE, Vinco M, Sanders D, Zhu Z, Ciampi R, Roh M, Shedden K, Gauger P, Doherty G, Thompson NW, Hanash S, Koenig RJ, Nikiforov YE (2005) Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene 24:6646-6656PubMedCrossRefGoogle Scholar
  32. Goellner JR, Gharib H, Grant CS, Johnson DA (1987) Fine needle aspiration cytology of the thyroid 1980 to 1986. Acta Cytol 31:587-590PubMedGoogle Scholar
  33. Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286:531-537PubMedCrossRefGoogle Scholar
  34. Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, Morrow M (eds) (2002) AJCC cancer staging manual. Springer, New YorkGoogle Scholar
  35. Greenlee RT, Hill-Harmon MB, Murray T, Thun M (2001) Cancer statistics. CA Cancer J Clin 51:15-36PubMedCrossRefGoogle Scholar
  36. Griffith OL, Melck A, Jones SJ, Wiseman SM (2006) Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers. J Clin Oncol 24:5043-5051PubMedCrossRefGoogle Scholar
  37. Hamada A, Mankovskaya S, Saenko V, Rogounovitch T, Mine M, Namba H, Nakashima M, Demidchik Y, Demidchik E, Yamashita S (2005) Diagnostic usefulness of PCR profiling of the differentially expressed marker genes in thyroid papillary carcinomas. Cancer Lett 224:289-301PubMedCrossRefGoogle Scholar
  38. Harach HR, Franssila KO, Wasenius VM (1985) Occult papillary carcinoma of the thyroid. A “normal” finding in Finland. A systematic autopsy study. Cancer 56:531-538PubMedCrossRefGoogle Scholar
  39. Hawthorn L, Stein L, Varma R, Wiseman S, Loree T, Tan D (2004) TIMP1 and SERPIN-A overexpression and TFF3 and CRABP1 underexpression as biomarkers for papillary thyroid carcinoma. Head Neck 26:1069-1083PubMedCrossRefGoogle Scholar
  40. Hesse E, Musholt PB, Potter E, Petrich T, Wehmeier M, von Wasielewski R, Lichtinghagen R, Musholt TJ (2005) Oncofoetal fibronectin - a tumour-specific marker in detecting minimal residual disease in differentiated thyroid carcinoma. Br J Cancer 93:565-570PubMedCrossRefGoogle Scholar
  41. Huang Y, Prasad M, Lemon WJ, Hampel H, Wright FA, Kornacker K, LiVolsi V, Frankel W, Kloos RT, Eng C, Pellegata NS, de la Chapelle A (2001) Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci U S A 98:15044-15049PubMedCrossRefGoogle Scholar
  42. Huang Y, de la Chapelle A, Pellegata NS (2003) Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma. Int J Cancer 104:735-744PubMedCrossRefGoogle Scholar
  43. Jarzab B, Wiench M, Fujarewicz K, Simek K, Jarzab M, Oczko-Wojciechowska M, Wloch J, Czarniecka A, Chmielik E, Lange D, Pawlaczek A, Szpak S, Gubala E, Swierniak A (2005) Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications. Cancer Res 65:1587-1597PubMedCrossRefGoogle Scholar
  44. Lazar V, Bidart JM, Caillou B, Mahe C, Lacroix L, Filetti S, Schlumberger M (1999) Expression of the Na+/I symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. J Clin Endocrinol Metab 84:3228-3234PubMedCrossRefGoogle Scholar
  45. Lee ML, Kuo FC, Whitmore GA, Sklar J (2000) Importance of replication in microarray gene expression studies: statistical methods and evidence from repetitive cDNA hybridizations. Proc Natl Acad Sci U S A 97:9834-9839PubMedCrossRefGoogle Scholar
  46. Liu FT, Rabinovich GA (2005) Galectins as modulators of tumour progression. Nat Rev Cancer 5:29-41PubMedCrossRefGoogle Scholar
  47. Liu W, Asa SL, Ezzat S (2005) 1alpha, 25-dihydroxyvitamin D3 targets PTEN-dependent fibronectin expression to restore thyroid cancer cell adhesiveness. Mol Endocrinol 19:2349-2357PubMedCrossRefGoogle Scholar
  48. LiVolsi VA, Asa SL (1994) The demise of follicular carcinoma of the thyroid gland. Thyroid 4:233-236PubMedCrossRefGoogle Scholar
  49. Lubitz CC, Gallagher LA, Finley DJ, Zhu B, Fahey TJ III (2005) Molecular analysis of minimally invasive follicular carcinomas by gene profiling. Surgery 138:1042-1048PubMedCrossRefGoogle Scholar
  50. Lubitz CC, Ugras SK, Kazam JJ, Zhu B, Scognamiglio T, Chen YT, Fahey TJ III (2006) Microarray analysis of thyroid nodule fine-needle aspirates accurately classifies benign and malignant lesions. J Mol Diagn 8:490-498PubMedCrossRefGoogle Scholar
  51. Maeta H, Ohgi S, Terada T (2001) Protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in papillary thyroid carcinomas. Virchows Arch 438:121-128PubMedCrossRefGoogle Scholar
  52. Mazzanti C, Zeiger MA, Costourous N, Umbricht C, Westra WH, Smith D, Somervell H, Bevilacqua G, Alexander HR, Libutti SK (2004) Using gene expression profiling to differentiate benign versus malignant thyroid tumors. Cancer Res 64:2898-2903PubMedCrossRefGoogle Scholar
  53. McHenry CR, Sandoval BA (1998) Management of follicular and Hürthle cell neoplasms of the thyroid gland. Surg Oncol Clin N Am 7:893-910PubMedGoogle Scholar
  54. Mecham BH, Klus GT, Strovel J, Augustus M, Byrne D, Bozso P, Wetmore DZ, Mariani TJ, Kohane IS, Szallasi Z (2004) Sequence-matched probes produce increased cross-platform consistency and more reproducible biological results in microarray-based gene expression measurements. Nucleic Acids Res 32:e74PubMedCrossRefGoogle Scholar
  55. Melck AL, Masoudi H, Griffith OL, Rajput A, Wilkins GE, Bugis S, Jones S, Wiseman SM (2007) Cell cycle regulators show diagnostic and prognostic utility for differentiated thyroid cancer. Ann Surg Oncol 14:3403-3411Google Scholar
  56. Mocellin S, Rossi CR (2007) Principles of gene microarray data analysis. Adv Exp Med Biol 593:19-30PubMedCrossRefGoogle Scholar
  57. Nakamura N, Erickson LA, Jin L, Kajita S, Zhang H, Qian X, Rumilla K, Lloyd RV (2006) Immunohistochemical separation of follicular variant of papillary thyroid carcinoma from follicular adenoma. Endocr Pathol 17:213-223PubMedCrossRefGoogle Scholar
  58. Nasir A, Chaudhry AZ, Gillespie J, Kaiser HE (2000) Papillary microcarcinoma of the thyroid: a clinico-pathologic and prognostic review. In Vivo 14:367-376PubMedGoogle Scholar
  59. Ng P, Tan JJ, Ooi HS, Lee YL, Chiu KP, Fullwood MJ, Srinivasan KG, Perbost C, Du L, Sung WK, Wei CL, Ruan Y (2006) Multiplex sequencing of paired-end ditags (MS-PET): a strategy for the ultra-high-throughput analysis of transcriptomes and genomes. Nucleic Acids Res 34:e84PubMedCrossRefGoogle Scholar
  60. O’Donovan N, Fischer A, Abdo EM, Simon F, Peter HJ, Gerber H, Buergi U, Marti U (2002) Differential expression of IgG Fc binding protein (FcgammaBP) in human normal thyroid tissue, thyroid adenomas and thyroid carcinomas. J Endocrinol 174:517-524PubMedCrossRefGoogle Scholar
  61. Onda M, Emi M, Yoshida A, Miyamoto S, Akaishi J, Asaka S, Mizutani K, Shimizu K, Nagahama M, Ito K, Tanaka T, Tsunoda T (2004) Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25 344 genes. Endocr Relat Cancer 11:843-854PubMedCrossRefGoogle Scholar
  62. Pauws E, Veenboer GJ, de Smit JW, Vijlder JJ, Morreau H, Ris-Stalpers C (2004) Genes differentially expressed in thyroid carcinoma identified by comparison of SAGE expression profiles. FASEB J 18:560-561PubMedGoogle Scholar
  63. Perez-Diez A, Morgun A, Shulzhenko N (2007) Microarrays for cancer diagnosis and classification. Adv Exp Med Biol 593:74-85PubMedCrossRefGoogle Scholar
  64. Pleasance ED, Jones SJM (2005) Evaluation of SAGE tags for transcriptome study. In: SM Wang (ed) SAGE technologies: current technologies and applications. Norwich, UK, Horizon BioscienceGoogle Scholar
  65. Poblete MT, Nualart F, del Pozo M, Perez JA, Figueroa CD (1996) Alpha 1-antitrypsin expression in human thyroid papillary carcinoma. Am J Surg Pathol 20:956-963PubMedCrossRefGoogle Scholar
  66. Porter DA, Krop IE, Nasser S, Sgroi D, Kaelin CM, Marks JR, Riggins G, Polyak K (2001) A SAGE (serial analysis of gene expression) view of breast tumor progression. Cancer Res 61:5697-5702PubMedGoogle Scholar
  67. Pounds SB (2006) Estimation and control of multiple testing error rates for microarray studies. Brief Bioinform 7:25-36PubMedCrossRefGoogle Scholar
  68. Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, de la Chapelle A, Kloos RT (2005) Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 18:48-57PubMedCrossRefGoogle Scholar
  69. Provenzano M, Mocellin S (2007) Complementary techniques: validation of gene expression data by quantitative real time PCR. Adv Exp Med Biol 593:66-73PubMedCrossRefGoogle Scholar
  70. Quackenbush J (2005) Using DNA microarrays to assay gene expression. In: Baxevanis AD, Ouellette BFF (eds) Bioinformatics: a practical guide to the analysis of genes and proteins. Wiley-Interscience, Hoboken, NJ, pp 409-444Google Scholar
  71. Ramirez R, Hsu D, Patel A, Fenton C, Dinauer C, Tuttle RM, Francis GL (2000) Over-expression of hepatocyte growth factor/scatter factor (HGF/SF) and the HGF/SF receptor (cMET) are associated with a high risk of metastasis and recurrence for children and young adults with papillary thyroid carcinoma. Clin Endocrinol (Oxf) 53:635-644CrossRefGoogle Scholar
  72. Ravetto C, Colombo L, Dottorini ME (2000) Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma: a retrospective study in 37,895 patients. Cancer 90:357-363PubMedCrossRefGoogle Scholar
  73. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM (2004) Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc Natl Acad Sci U S A 101:9309-9314PubMedCrossRefGoogle Scholar
  74. Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs BB, Barrette TR, Anstet MJ, Kincead-Beal C, Kulkarni P, Varambally S, Ghosh D, Chinnaiyan AM (2007) Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia 9:166-180PubMedCrossRefGoogle Scholar
  75. Rosen J, He M, Umbricht C, Alexander HR, Dackiw AP, Zeiger MA, Libutti SK (2005) A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression. Surgery 138:1050-1056PubMedCrossRefGoogle Scholar
  76. Rubin MA, Zhou M, Dhanasekaran SM, Varambally S, Barrette TR, Sanda MG, Pienta KJ, Ghosh D, Chinnaiyan AM (2002) Alpha-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. JAMA 287:1662-1670PubMedCrossRefGoogle Scholar
  77. Scognamiglio T, Hyjek E, Kao J, Chen YT (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 126:700-708PubMedCrossRefGoogle Scholar
  78. Segev DL, Clark DP, Zeiger MA, Umbricht C (2003) Beyond the suspicious thyroid fine needle aspirate. A Rev Acta Cytol 47:709-722CrossRefGoogle Scholar
  79. Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP, Rosenbaum AM, Wang MD, Zhang K, Mitra RD, Church GM (2005) Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309:1728-1732PubMedCrossRefGoogle Scholar
  80. Shih W, Chetty R, Tsao MS (2005) Expression profiling by microarrays in colorectal cancer (review). Oncol Rep 13:517-524PubMedGoogle Scholar
  81. Siddiqui AS, Delaney AD, Schnerch A, Griffith OL, Jones SJ, Marra MA (2006) Sequence biases in large scale gene expression profiling data. Nucleic Acids Res 34:e83PubMedCrossRefGoogle Scholar
  82. Steinhoff C, Vingron M (2006) Normalization and quantification of differential expression in gene expression microarrays. Brief Bioinform 7:166-177PubMedCrossRefGoogle Scholar
  83. Takano T, Hasegawa Y, Matsuzuka F, Miyauchi A, Yoshida H, Higashiyama T, Kuma K, Amino N (2000) Gene expression profiles in thyroid carcinomas. Br J Cancer 83:1495-1502PubMedCrossRefGoogle Scholar
  84. Takano T, Miyauchi A, Yoshida H, Kuma K, Amino N (2005) Decreased relative expression level of trefoil factor 3 mRNA to galectin-3 mRNA distinguishes thyroid follicular carcinoma from adenoma. Cancer Lett 219:91-96PubMedCrossRefGoogle Scholar
  85. Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 98:5116-5121PubMedCrossRefGoogle Scholar
  86. Verhaak RG, Staal FJ, Valk PJ, Lowenberg B, Reinders MJ, de Ridder D (2006) The effect of oligonucleotide microarray data pre-processing on the analysis of patient-cohort studies. BMC Bioinformatics 7:105PubMedCrossRefGoogle Scholar
  87. Visone R, Pallante P, Vecchione A, Cirombella R, Ferracin M, Ferraro A, Volinia S, Coluzzi S, Leone V, Borbone E, Liu CG, Petrocca F, Troncone G, Calin GA, Scarpa A, Colato C, Tallini G, Santoro M, Croce CM, Fusco A (2007) Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene 26:7590-7595Google Scholar
  88. Wasenius VM, Hemmer S, Kettunen E, Knuutila S, Franssila K, Joensuu H (2003) Hepatocyte growth factor receptor, matrix metalloproteinase-11, tissue inhibitor of metalloproteinase-1, and fibronectin are up-regulated in papillary thyroid carcinoma: a cDNA and tissue microarray study. Clin Cancer Res 9:68-75PubMedGoogle Scholar
  89. Weber F, Shen L, Aldred MA, Morrison CD, Frilling A, Saji M, Schuppert F, Broelsch CE, Ringel MD, Eng C (2005) Genetic Classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination. J Clin Endo Metab 90:2512-2521CrossRefGoogle Scholar
  90. Wiseman SM, Baliski C, Irvine R, Anderson D, Wilkins G, Filipenko D, Zhang H, Bugis S (2006) Hemithyroidectomy: The optimal initial surgical approach for individuals undergoing surgery for a cytological diagnosis of follicular neoplasm. Ann Surg Oncol 13:425-432PubMedCrossRefGoogle Scholar
  91. Wu Z, Irizarry RA, Gentleman R, Martinez-Murillo F, Spencer F (2004) A model-based background adjustment for oligonucleotide expression arrays. J Am Stat Assoc 99:909-917CrossRefGoogle Scholar
  92. Yano Y, Uematsu N, Yashiro T, Hara H, Ueno E, Miwa M, Tsujimoto G, Aiyoshi Y, Uchida K (2004) Gene expression profiling identifies platelet-derived growth factor as a diagnostic molecular marker for papillary thyroid carcinoma. Clin Cancer Res 10:2035-2043PubMedCrossRefGoogle Scholar
  93. Yauk CL, Berndt ML (2007) Review of the literature examining the correlation among DNA microarray technologies. Environ Mol Mutagen 48:380-94Google Scholar
  94. Zou M, Famulski KS, Parhar RS, Baitei E, Al-Mohanna FA, Farid NR, Shi Y (2004) Microarray analysis of metastasis-associated gene expression profiling in a murine model of thyroid carcinoma pulmonary metastasis: identification of S100A4 (Mts1) gene overexpression as a poor prognostic marker for thyroid carcinoma. J Clin Endocrinol Metab 89:6146-6154PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Obi L. Griffith
    • 1
  • Adrienne Melck
    • 2
  • Steven J. M. Jones
    • 1
  • Sam M. Wiseman
    • 3
  1. 1.Michael Smith Genome Sciences Center, British Columbia Cancer AgencyVancouverCanada
  2. 2.Department of SurgeryUniversity of British ColumbiaVancouverCanada
  3. 3.Department of SurgerySaint Paul’s HospitalVancouverCanada

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