Molecular determination of benign and malignant thyroid tumors

References

• Volzke H, Ludemann J, Robinson DM et al. The prevalence of undiagnosed thyroid disorders in a previously iodine-deficient area. Thyroid13, 803–810 (2003).
   PubMed Web of Science ®Google Scholar
• Reiners C, Wegscheider K, Schicha H et al. Prevalence of thyroid disorders in the working population of Germany: ultrasonography screening in 96,278 unselected employees. Thyroid14, 926–932 (2004).
   PubMed Web of Science ®Google Scholar
• Hegedus L, Bonnema SJ, Bennedbaek FN. Management of simple nodular goiter: current status and future perspectives. Endocr. Rev.24, 102–132 (2003).
   PubMed Web of Science ®Google Scholar
• Hegedus L. Clinical practice. The thyroid nodule. N. Engl. J. Med.351, 1764–1771 (2004).
   PubMed Web of Science ®Google Scholar
• Krohn K, Fuhrer D, Bayer Y et al. Molecular pathogenesis of euthyroid and toxic multinodular goiter. Endocr. Rev.26, 504–524 (2005).
   Google Scholar
• DeLellis R, Lloyd RV, Heitz H, Eng C. World Health Organization Classification of Tumors. Pathology and genetics of tumors of endocrine organs. IARC Press, Lyon, France (2004).
   Google Scholar
• Krohn K, Wohlgemuth S, Gerber H, Paschke R. Hot microscopic areas of iodine-deficient euthyroid goitres contain constitutively activating TSH receptor mutations. J. Pathol.192, 37–42 (2000).
   Google Scholar
• Namba H, Matsuo K, Fagin JA. Clonal composition of benign and malignant human thyroid tumors. J. Clin. Invest.86, 120–125 (1990).
   Google Scholar
• Aeschimann S, Kopp PA, Kimura ET et al. Morphological and functional polymorphism within clonal thyroid nodules. J. Clin. Endocrinol. Metab.77, 846–851 (1993).
   Google Scholar
• Bond JA, Haughton MF, Rowson JM et al. Control of replicative life span in human cells: barriers to clonal expansion intermediate between M1 senescence and M2 crisis. Mol. Cell. Biol.19, 3103–3114 (1999).
   PubMedGoogle Scholar
• Krohn K, Reske A, Ackermann F, Muller A, Paschke R. Ras mutations are rare in solitary cold and toxic thyroid nodules. Clin. Endocrinol. (Oxf.)55, 241–248 (2001).
   Google Scholar
• Fagin JA. Minireview: branded from the start-distinct oncogenic initiating events may determine tumor fate in the thyroid. Mol. Endocrinol.16, 903–911 (2002).
   PubMedGoogle Scholar
• Krohn K, Paschke R. Clinical review 133: progress in understanding the etiology of thyroid autonomy. J. Clin. Endocrinol. Metab.86, 3336–3345 (2001).
   PubMed Web of Science ®Google Scholar
• Fuhrer D, Krohn K, Paschke R. Toxic adenom and toxic multinodular goiter. In: Werner & Ingbar’s The Thyroid: A Fundamental And Clinical Text, Ninth Edition.Lippincott Williams & Wilkins, PA, USA (2005).
   Google Scholar
• Parma J, Duprez L, Van Sande J et al. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature365, 649–651 (1993).
   PubMed Web of Science ®Google Scholar
• Kimura T, Van Keymeulen A, Golstein J, Fusco A, Dumont JE, Roger PP. Regulation of thyroid cell proliferation by TSH and other factors: a critical evaluation of in vitro models. Endocr. Rev.22, 631–656 (2001).
   PubMed Web of Science ®Google Scholar
• Trulzsch B, Krohn K, Wonerow P et al. Detection of thyroid-stimulating hormone receptor and Gsα mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis. J. Mol. Med.78, 684–691 (2001).
   Google Scholar
• Parma J, Duprez L, Van Sande J et al. Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs α genes as a cause of toxic thyroid adenomas. J. Clin. Endocrinol. Metab.82, 2695–2701 (1997).
   PubMed Web of Science ®Google Scholar
• Fuhrer D, Lachmund P, Nebel IT, Paschke R. The thyrotropin receptor mutation database: update (2003). Thyroid13, 1123–1126 (2003).
   Google Scholar
• Duprez L, Hermans J, Van Sande J, Dumont JE, Vassart G, Parma J. Two autonomous nodules of a patient with multinodular goiter harbor different activating mutations of the thyrotropin receptor gene. J. Clin. Endocrinol. Metab.82, 306–308 (1997).
   Google Scholar
• Holzapfel HP, Fuhrer D, Wonerow P, Weinland G, Scherbaum WA, Paschke R. Identification of constitutively activating somatic thyrotropin receptor mutations in a subset of toxic multinodular goiters. J. Clin. Endocrinol. Metab.82, 4229–4233 (1997).
   Google Scholar
• Trulzsch B, Krohn K, Wonerow P. Detection of thyroid-stimulating hormone receptor and Gsα mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis. J. Mol. Med.78, 684–691 (2001).
   Google Scholar
• Vanvooren V, Uchino S, Duprez L et al. Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population. Eur. J. Endocrinol.147, 287–291 (2002).
   Google Scholar
• Krohn K, Fuhrer D, Holzapfel HP, Paschke R. Clonal origin of toxic thyroid nodules with constitutively activating thyrotropin receptor mutations. J. Clin. Endocrinol. Metab.83, 130–134 (1998).
   Google Scholar
• Fuhrer D, Mix M, Willgerodt H et al. Autosomal dominant nonautoimmune hyperthyroidism. Clinical features-diagnosis-therapy. Exp. Clin. Endocrinol. Diabetes106(Suppl. 4), S10–S15 (1998).
   Google Scholar
• Duprez L, Parma J, Van Sande J et al. Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. Nat. Genet.7, 396–401 (1994).
   PubMed Web of Science ®Google Scholar
• Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N. Engl. J. Med.325, 1688–1695 (1991).
   PubMed Web of Science ®Google Scholar
• Feuillan PP, Shawker T, Rose SR, Jones J, Jeevanram RK, Nisula BC. Thyroid abnormalities in the McCune-Albright syndrome: ultrasonography and hormonal studies. J. Clin. Endocrinol. Metab.71, 1596–1601 (1990).
   Google Scholar
• Zeiger MA, Saji M, Gusev Y et al. Thyroid-specific expression of cholera toxin A1 subunit causes thyroid hyperplasia and hyperthyroidism in transgenic mice. Endocrinology138, 3133–3140 (1997).
   PubMed Web of Science ®Google Scholar
• Ledent C, Coppee F, Dumont JE, Vassart G, Parmentier M. Transgenic models for proliferative and hyperfunctional thyroid diseases. Exp. Clin. Endocrinol. Diabetes104(Suppl. 3), 43–46 (1996).
   Google Scholar
• Ledent C, Dumont JE, Vassart G, Parmentier M. Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism. EMBO J.11, 537–542 (1992).
   PubMed Web of Science ®Google Scholar
• Michiels FM, Caillou B, Talbot M et al. Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice. Proc. Natl Acad. Sci. USA91, 10488–10492 (1994).
   PubMed Web of Science ®Google Scholar
• Fuhrer D, Lewis MD, Alkhafaji F et al. Biological activity of activating thyroid-stimulating hormone receptor mutants depends on the cellular context. Endocrinology144, 4018–4030 (2003).
   Google Scholar
• Fusco A, Grieco M, Santoro M et al. A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases. Nature328, 170–172 (1987).
   PubMed Web of Science ®Google Scholar
• Grieco M, Santoro M, Berlingieri MT et al. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell60, 557–563 (1990).
   PubMed Web of Science ®Google Scholar
• Santoro M, Melillo RM, Carlomagno F, Vecchio G, Fusco A. Minireview: RET: normal and abnormal functions. Endocrinology145, 5448–5451 (2004).
   PubMed Web of Science ®Google Scholar
• Jhiang SM. The RET proto-oncogene in human cancers. Oncogene19, 5590–5597 (2000).
   PubMed Web of Science ®Google Scholar
• Fagin JA. Challenging dogma in thyroid cancer molecular genetics – role of RET/PTC and BRAF in tumor initiation. J. Clin. Endocrinol. Metab.89, 4264–4266 (2004).
   PubMed Web of Science ®Google Scholar
• Jhiang SM, Sagartz JE, Tong Q et al. Targeted expression of the ret/PTC1 oncogene induces papillary thyroid carcinomas. Endocrinology137, 375–378 (1996).
   PubMed Web of Science ®Google Scholar
• Nikiforova MN, Stringer JR, Blough R, Medvedovic M, Fagin JA, Nikiforov YE. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science290, 138–141 (2000).
   PubMed Web of Science ®Google Scholar
• Caudill CM, Zhu Z, Ciampi R, Stringer JR, Nikiforov YE. Dose-dependent generation of RET/PTC in human thyroid cells after in vitro exposure to γ-radiation: a model of carcinogenic chromosomal rearrangement induced by ionizing radiation. J. Clin. Endocrinol. Metab.90, 2364–2369 (2005).
   PubMed Web of Science ®Google Scholar
• Powell DJ Jr, Russell J, Nibu K et al. The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids. Cancer Res.58, 5523–5528 (1998).
   PubMed Web of Science ®Google Scholar
• Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. 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.63, 1454–1457 (2003).
   PubMed Web of Science ®Google Scholar
• Nikiforova MN, Kimura ET, Gandhi M et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J. Clin. Endocrinol. Metab.88, 5399–5404 (2003).
   PubMed Web of Science ®Google Scholar
• Namba H, Nakashima M, Hayashi T et al. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J. Clin. Endocrinol. Metab.88, 4393–4397 (2003).
   PubMed Web of Science ®Google Scholar
• Kumagai A, Namba H, Saenko VA et al. Low frequency of BRAFT1796A mutations in childhood thyroid carcinomas. J. Clin. Endocrinol. Metab.89, 4280–4284 (2004).
   PubMedGoogle Scholar
• Giordano TJ, Kuick R, Thomas DG et al. Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene24(44), 6646–6656 (2005).
   PubMed Web of Science ®Google Scholar
• Melillo RM, Castellone MD, Guarino V et al. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J. Clin. Invest.115, 1068–1081 (2005).
   PubMed Web of Science ®Google Scholar
• Mitsutake N, Miyagishi M, Mitsutake S et al. BRAF mediates RET/PTC-induced MAPK activation in thyroid cells: functional support for requirement of the RET/PTC-RAS-BRAF pathway in papillary thyroid carcinogenesis. Endocrinology147(2), 1472–1049 (2006).
   Google Scholar
• Wan PT, Garnett MJ, Roe SM et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell116, 855–867 (2004).
   PubMed Web of Science ®Google Scholar
• Nikiforova MN, Ciampi R, Salvatore G et al. Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas. Cancer Lett.209, 1–6 (2004).
   PubMedGoogle Scholar
• Lima J, Trovisco V, Soares P et al. BRAF mutations are not a major event in post-Chernobyl childhood thyroid carcinomas. J. Clin. Endocrinol. Metab.89, 4267–4271 (2004).
   PubMed Web of Science ®Google Scholar
• Knauf JA, Ma X, Smith EP et al. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res.65, 4238–4245 (2005).
   PubMed Web of Science ®Google Scholar
• Ciampi R, Knauf JA, Kerler R et al. Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J. Clin. Invest.115, 94–101 (2005).
   PubMed Web of Science ®Google Scholar
• Ciampi R, Nikiforov YE. RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis. Endocrinology (2006) (Epub ahead of print).
   Google Scholar
• Frattini M, Ferrario C, Bressan P et al. Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene23, 7436–7440 (2004).
   PubMed Web of Science ®Google Scholar
• Fagin JA. Perspective: lessons learned from molecular genetic studies of thyroid cancer – insights into pathogenesis and tumor-specific therapeutic targets. Endocrinology143, 2025–2028 (2002).
   PubMed Web of Science ®Google Scholar
• Eszlinger M, Krohn K, Frenzel R, Kropf S, Tonjes A, Paschke R. Gene expression analysis reveals evidence for inactivation of the TGF-β signaling cascade in autonomously functioning thyroid nodules. Oncogene23, 795–804 (2004).
   Google Scholar
• Castro P, Eknaes M, Teixeira MR et al. Adenomas and follicular carcinomas of the thyroid display two major patterns of chromosomal changes. J. Pathol.206, 305–311 (2005).
   PubMed Web of Science ®Google Scholar
• Sobrinho-Simoes M, Preto A, Rocha AS et al. Molecular pathology of well-differentiated thyroid carcinomas. Virchows Arch.447, 787–793 (2005).
   PubMedGoogle Scholar
• Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry JF, de Micco C. Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J. Clin. Endocrinol. Metab.88, 2745–2752 (2003).
   PubMed Web of Science ®Google Scholar
• Rochefort P, Caillou B, Michiels FM et al. Thyroid pathologies in transgenic mice expressing a human activated Ras gene driven by a thyroglobulin promoter. Oncogene12, 111–118 (1996).
   Google Scholar
• Santelli G, de Franciscis V, Portella G et al. Production of transgenic mice expressing the Ki-ras oncogene under the control of a thyroglobulin promoter. Cancer Res.53, 5523–5527 (1993).
   PubMed Web of Science ®Google Scholar
• Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am. J. Clin. Pathol.120, 71–77 (2003).
   PubMed Web of Science ®Google Scholar
• Kroll TG, Sarraf P, Pecciarini L et al. PAX8–PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science289, 1357–1360 (2000).
   PubMed Web of Science ®Google Scholar
• Gregory PJ, Wang X, Allard BL et al. The PAX8/PPARγ fusion oncoprotein transforms immortalized human thyrocytes through a mechanism probably involving wild-type PPARgamma inhibition. Oncogene23, 3634–3641 (2004).
   Google Scholar
• Au AY, McBride C, Wilhelm KG, Jr. et al. PAX8-peroxisome proliferator-activated receptor γ (PPARγ) disrupts normal pax8 or pparγ transcriptional function and stimulates follicular thyroid cell growth. Endocrinology147, 367–376 (2006).
   Google Scholar
• Cheung L, Messina M, Gill A et al. Detection of the PAX8–PPAR γ fusion oncogene in both follicular thyroid carcinomas and adenomas. J. Clin. Endocrinol. Metab.88, 354–357 (2003).
   PubMed Web of Science ®Google Scholar
• Marques AR, Espadinha C, Catarino AL et al. Expression of PAX8-PPAR γ 1 rearrangements in both follicular thyroid carcinomas and adenomas. J. Clin. Endocrinol. Metab.87, 3947–3952 (2002).
   PubMed Web of Science ®Google Scholar
• Nikiforova MN, Biddinger PW, Caudill CM, Kroll TG, Nikiforov YE. PAX8–PPARγ rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses. Am. J. Surg. Pathol.26, 1016–1023 (2002).
   PubMed Web of Science ®Google Scholar
• 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.88, 2318–2326 (2003).
   PubMed Web of Science ®Google Scholar
• Xing M, Westra WH, Tufano RP et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J. Clin. Endocrinol. Metab.90, 6373–6379 (2005).
   PubMed Web of Science ®Google Scholar
• Garcia-Rostan G, Costa AM, Pereira-Castro I et al. Mutation of the PIK3CA gene in anaplastic thyroid cancer. Cancer Res.65, 10199–10207 (2005).
   PubMed Web of Science ®Google Scholar
• Moretti F, Farsetti A, Soddu S et al. p53 re-expression inhibits proliferation and restores differentiation of human thyroid anaplastic carcinoma cells. Oncogene14, 729–740 (1997).
   PubMed Web of Science ®Google Scholar
• Fagin JA, Matsuo K, Karmakar A, Chen DL, Tang SH, Koeffler HP. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J. Clin. Invest.91, 179–184 (1993).
   PubMed Web of Science ®Google Scholar
• Rao AS, Kremenevskaja N, von Wasielewski R et al. Wnt/β-catenin signalling mediates anti-neoplastic effects of Imatinib mesylate (Glivec) in anaplastic thyroid cancer. J. Clin. Endocrinol. Metab.91(1), 159–168 (2005).
   Google Scholar
• Wynford-Thomas D, Jones CJ, Wyllie FS. The tumour suppressor gene p53 as a regulator of proliferative life-span and tumour progression. Biol. Signals5, 139–153 (1996).
   PubMedGoogle Scholar
• Krohn K, Eszlinger M, Paschke R, Roeder I, Schuster E. Increased power of microarray analysis by use of an algorithm based on a multivariate procedure. Bioinformatics21, 3530–3534 (2005).
   Google Scholar
• Eszlinger M, Wiench M, Jarzab B et al. Meta- and reanalysis of gene expression profiles of hot and cold thyroid nodules and papillary thyroid carcinoma for gene groups. J. Clin. Endocrinol. Metab.91(5), 1934–1942 (2006).
   Google Scholar
• Jarzab B, Wiench M, Fujarewicz K et al. Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications. Cancer Res.65, 1587–1597 (2005).
   PubMed Web of Science ®Google Scholar
• Huang Y, Prasad M, Lemon WJ et al. Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc. Natl Acad. Sci. USA98, 15044–15049 (2001).
   PubMed Web of Science ®Google Scholar
• Aldred MA, Huang Y, Liyanarachchi S et al. 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, 3531–3539 (2004).
   Google Scholar
• Wreesmann VB, Ghossein RA, Hezel M et al. Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity. Genes Chromosomes Cancer40, 355–364 (2004).
   Google Scholar
• Giordano TJ, Au AY, Kuick R et al. Delineation, functional validation, and bioinformatic evaluation of gene expression in thyroid follicular carcinomas with the PAX8-PPARG translocation. Clin. Cancer Res.12, 1983–1993 (2006).
   PubMedGoogle Scholar
• Lacroix L, Lazar V, Michiels S et al. Follicular thyroid tumors with the PAX8–PPARγ1 rearrangement display characteristic genetic alterations. Am. J. Pathol.167, 223–231 (2005).
   PubMed Web of Science ®Google Scholar
• Lui WO, Foukakis T, Liden J et al. Expression profiling reveals a distinct transcription signature in follicular thyroid carcinomas with a PAX8-PPAR(γ) fusion oncogene. Oncogene24, 1467–1476 (2005).
   PubMedGoogle Scholar
• Aldred MA, Morrison C, Gimm O et al. Peroxisome proliferator-activated receptor γ is frequently downregulated in a diversity of sporadic nonmedullary thyroid carcinomas. Oncogene22, 3412–3416 (2003).
   Google Scholar
• Eszlinger M, Krohn K, Berger K et al. Gene expression analysis reveals evidence for increased expression of cell cycle-associated genes and Gq-protein-protein kinase C signaling in cold thyroid nodules. J. Clin. Endocrinol. Metab.90, 1163–1170 (2005).
   Google Scholar
• Eszlinger M, Krohn K, Paschke R. 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, 4834–4842 (2001).
   Google Scholar
• Jarzab B, Wodak SJ, Lapi P et al. The distance between histotypes of differentiated thyroid cancer: gene expression profiling study. Thyroid, 13th International Thyroid Congress (Abstract). (2005).
   Google Scholar
• 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.90, 2512–2521 (2005).
   PubMed Web of Science ®Google Scholar
• Baris O, Mirebeau-Prunier D, Savagner F et al. Gene profiling reveals specific oncogenic mechanisms and signaling pathways in oncocytic and papillary thyroid carcinoma. Oncogene24, 4155–4161 (2005).
   Google Scholar
• Jacques C, Baris O, Prunier-Mirebeau D et al. Two-step differential expression analysis reveals a new set of genes involved in thyroid oncocytic tumors. J. Clin. Endocrinol. Metab.90, 2314–2320 (2005).
   Google Scholar
• Onda M, Emi M, Yoshida A et al. Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25 344 genes. Endocr. Relat. Cancer11, 843–854 (2004).
   PubMed Web of Science ®Google Scholar
• Yano Y, Uematsu N, Yashiro T et al. Gene expression profiling identifies platelet-derived growth factor as a diagnostic molecular marker for papillary thyroid carcinoma. Clin. Cancer Res.10, 2035–2043 (2004).
   PubMedGoogle Scholar
• Aldred MA, Ginn-Pease ME, Morrison CD et al. Caveolin-1 and caveolin-2, together with three bone morphogenetic protein-related genes, may encode novel tumor suppressors down-regulated in sporadic follicular thyroid carcinogenesis. Cancer Res.63, 2864–2871 (2003).
   PubMed Web of Science ®Google Scholar
• Barden CB, Shister KW, Zhu B et al. Classification of follicular thyroid tumors by molecular signature: results of gene profiling. Clin. Cancer Res.9, 1792–1800 (2003).
   PubMed Web of Science ®Google Scholar
• Takano T, Miyauchi A, Yoshida H, Kuma K, Amino N. Decreased relative expression level of trefoil factor 3 mRNA to galectin-3 mRNA distinguishes thyroid follicular carcinoma from adenoma. Cancer Lett.219, 91–96 (2005).
   Google Scholar
• Cerutti JM, Delcelo R, Amadei MJ et al. A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression. J. Clin. Invest.113, 1234–1242 (2004).
   PubMed Web of Science ®Google Scholar
• Krause K, Eszlinger M, Gimm O et al. TFF3 based candidate gene discrimination of benign and malignant thyroid tumours in a region with borderline iodine deficiency (Submitted).
   Google Scholar
• Nikiforov YE, Nikiforova MN, Gnepp DR, Fagin JA. Prevalence of mutations of ras and p53 in benign and malignant thyroid tumors from children exposed to radiation after the Chernobyl nuclear accident. Oncogene13, 687–693 (1996).
   Google Scholar
• Santoro M, Carlomagno F, Melillo RM, Fusco A. Dysfunction of the RET receptor in human cancer. Cell. Mol. Life Sci.61, 2954–2964 (2004).
   PubMedGoogle Scholar
• Brandi ML, Gagel RF, Angeli A et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J. Clin. Endocrinol. Metab.86, 5658–5671 (2001).
   PubMed Web of Science ®Google Scholar
• Podtcheko A, Ohtsuru A, Tsuda S et al. The selective tyrosine kinase inhibitor, STI571, inhibits growth of anaplastic thyroid cancer cells. J. Clin. Endocrinol. Metab.88, 1889–1896 (2003).
   Google Scholar
• Carlomagno F, Vitagliano D, Guida T et al. Efficient inhibition of RET/papillary thyroid carcinoma oncogenic kinases by 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2). J. Clin. Endocrinol. Metab.88, 1897–1902 (2003).
   PubMed Web of Science ®Google Scholar
• Park JW, Zarnegar R, Kanauchi H et al. Troglitazone, the peroxisome proliferator-activated receptor-γ agonist, induces antiproliferation and redifferentiation in human thyroid cancer cell lines. Thyroid15, 222–231 (2005).
   PubMed Web of Science ®Google Scholar
• Martelli ML, Iuliano R, Le P et al. Inhibitory effects of peroxisome poliferator-activated receptor γ on thyroid carcinoma cell growth. J. Clin. Endocrinol. Metab.87, 4728–4735 (2002).
   PubMed Web of Science ®Google Scholar
• Ouyang B, Knauf JA, Smith EP et al. Inhibitors of Raf kinase activity block growth of thyroid cancer cells with RET/PTC or BRAF mutations in vitro and in vivo. Clin. Cancer Res.12, 1785–1793 (2006).
   PubMed Web of Science ®Google Scholar
• Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S. 1985–1995 [see comments]. Cancer83, 2638–2648 (1998).
   PubMed Web of Science ®Google Scholar