Expression of ck-19, galectin-3 and hbme-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis

Diagnostic Pathology

Maria Aparecida da Silva Pinhal³  Auro Del Giglio¹  Michelle de Lima Farah⁴  Carolina Ogawa Matsubayashi⁴  Adriana Braz Del Giglio⁴  Leandro Luongo de Matos² 

[1] Chairman of Hematology and Oncology Department – Faculdade de Medicina do ABC, Santo André, Brazil; Medical Oncologist – Albert Einstein Jewish Hospital, São Paulo, Brazil;Rua São Paulo, 1670, Ap.41, ZIP: 09541-100, São Caetano do Sul, SP, Brazil;Biochemistry Department – Universidade Federal de São Paulo, São Paulo, Brazil;Medical School Students – Faculdade de Medicina do ABC, Santo André, Brazil

关键词: Review;    Thyroid;    HBME-1 antigen;    Keratin 19;    Galectin 3;    Biological;    Tumor markers;   

Others  :  808008
DOI  :  10.1186/1746-1596-7-97

 received in 2012-05-20, accepted in 2012-08-06,  发布年份 2012

【 摘 要 】

Background

To distinguish between malignant and benign lesions of the thyroid gland histological demonstration is often required since the fine-needle aspiration biopsy method applied pre-operatively has some limitations. In an attempt to improve diagnostic accuracy, markers using immunocytochemistry and immunohistochemistry techniques have been studied, mainly cytokeratin-19 (CK-19), galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1). However, current results remain controversial. The aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions.

Methods

A systematic review of published articles on MEDLINE and The Cochrane Library was performed. After establishing inclusion and exclusion criteria, 66 articles were selected. The technique of meta-analysis of diagnostic accuracy was employed and global values of sensitivity, specificity, area under the summary ROC curve, and diagnostic odds ratio (dOR) were calculated.

Results

For the immunohistochemistry technique, the positivity of CK-19 for the diagnosis of malignant thyroid lesions demonstrated global sensitivity of 81% and specificity of 73%; for Gal-3, sensitivity of 82% and specificity of 81%; and for HBME-1, sensitivity of 77% and specificity of 83%. The association of the three markers determined sensitivity of 85%, specificity of 97%, and diagnostic odds ratio of 95.1. Similar results were also found for the immunocytochemistry assay.

Conclusion

This meta-analysis demonstrated that the three immunomarkers studied are accurate in pre- and postoperative diagnosis of benign and malignant thyroid lesions. Nevertheless, the search for other molecular markers must continue in order to enhance this diagnostic accuracy since the results found still show a persistency of false-negative and false-positive tests.

Virtual slides

Http://www.diagnosticpathology.diagnomx.eu/vs/3436263067345159

【 授权许可】

   
2012 de Matos et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin 2010, 60:277-300.
• [2]Gonzalez-Yebra B, Peralta R, Gonzalez AL, Ayala-Garcia MA, de Zarate ME O, Salcedo M: Genetic alterations in a primary medullary thyroid carcinoma and its lymph node metastasis in a patient with 15 years follow-up. Diagn Pathol 2012, 7:63. BioMed Central Full Text
• [3]Peccin S, de Castsro JA, Furlanetto TW, Furtado AP, Brasil BA, Czepielewski MA: Ultrasonography: is it useful in the diagnosis of cancer in thyroid nodules? J Endocrinol Invest 2002, 25:39-43.
• [4]Tomimori EK, Bisi H, Medeiros-Neto G, Camargo RY: Ultrasonographic evaluation of thyroid nodules: comparison with cytologic and histologic diagnosis. Arq Bras Endocrinol Metabol 2004, 48:105-113.
• [5]Utiger RD: The multiplicity of thyroid nodules and carcinomas. N Engl J Med 2005, 352:2376-2378.
• [6]Schlumberger MJ: Papillary and follicular thyroid carcinoma. N Engl J Med 1998, 338:297-306.
• [7]LiVolsi VA, Baloch ZW: Follicular neoplasms of the thyroid: view, biases, and experiences. Adv Anat Pathol 2004, 11:279-287.
• [8]Zeiger MA, Dackiw AP: Follicular thyroid lesions, elements that affect both diagnosis and prognosis. J Surg Oncol 2005, 89:108-113.
• [9]Matsuo SE, Martins L, Leoni SG, Hajjar D, Ricarte-Filho JC, Ebina KN, Kimura ET: Biological markers in thyroid tumors. Arq Bras Endocrinol Metabol 2004, 48:114-125.
• [10]Barroeta JE, Baloch ZW, Lal P, Pasha TL, Zhang PJ, LiVolsi VA: 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 2006, 17:225-234.
• [11]Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, Livolsi VA, Mandel SJ, et al.: Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology. N Engl J Med 2012. Epub ahead of print
• [12]Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A: Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 2006, 6:31. BioMed Central Full Text
• [13]Jones CM, Athanasiou T: Summary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests. Ann Thorac Surg 2005, 79:16-20.
• [14]Hong Z, Qi JP, Wang YW, Song YJ, Zhang ZY: Hyalinizing trabecular tumor and papillary carcinoma of the thyroid. Chin Med J (Engl) 2010, 123:2832-2835.
• [15]Zhu X, Sun T, Lu H, Zhou X, Lu Y, Cai X: Diagnostic significance of CK19, RET, galectin-3 and HBME-1 expression for papillary thyroid carcinoma. J Clin Pathol 2010, 63:786-789.
• [16]Park YJ, Kwak SH, Kim DC, Kim H, Choe G, do Park J, Jang HC, Park SH, Cho BY, Park SY: 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 2007, 22:621-628.
• [17]Scognamiglio T, Hyjek E, Kao J, Chen YT: 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 2006, 126:700-708.
• [18]Nasr MR, Mukhopadhyay S, Zhang S, Katzenstein AL: Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: Utility of HBME1 combined with CK19 immunostaining. Mod Pathol 2006, 19:1631-1637.
• [19]Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, de la Chapelle A, Kloos RT: Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 2005, 18:48-57.
• [20]Cameron BR, Berean KW: Cytokeratin subtypes in thyroid tumours: immunohistochemical study with emphasis on the follicular variant of papillary carcinoma. J Otolaryngol 2003, 32:319-322.
• [21]Casey MB, Lohse CM, Lloyd RV: Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1. Endocr Pathol 2003, 14:55-60.
• [22]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.
• [23]Sahoo S, Hoda SA, Rosai J, DeLellis RA: Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma: a note of caution. Am J Clin Pathol 2001, 116:696-702.
• [24]Cheung CC, Ezzat S, Freeman JL, Rosen IB, Asa SL: Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol 2001, 14:338-342.
• [25]Barut F, Onak Kandemir N, Bektas S, Bahadir B, Keser S, Ozdamar SO: Universal markers of thyroid malignancies: galectin-3, HBME-1, and cytokeratin-19. Endocr Pathol 2010, 21:80-89.
• [26]Wiseman SM, Melck A, Masoudi H, Ghaidi F, Goldstein L, Gown A, Jones SJ, Griffith OL: Molecular phenotyping of thyroid tumors identifies a marker panel for differentiated thyroid cancer diagnosis. Ann Surg Oncol 2008, 15:2811-2826.
• [27]Liu YY, Morreau H, Kievit J, Romijn JA, Carrasco N, Smit JW: Combined immunostaining with galectin-3, fibronectin-1, CITED-1, Hector Battifora mesothelial-1, cytokeratin-19, peroxisome proliferator-activated receptor-{gamma}, and sodium/iodide symporter antibodies for the differential diagnosis of non-medullary thyroid carcinoma. Eur J Endocrinol 2008, 158:375-384.
• [28]Murphy KM, Chen F, Clark DP: Identification of immunohistochemical biomarkers for papillary thyroid carcinoma using gene expression profiling. Hum Pathol 2008, 39:420-426.
• [29]Nakamura N, Erickson LA, Jin L, Kajita S, Zhang H, Qian X, Rumilla K, Lloyd RV: Immunohistochemical separation of follicular variant of papillary thyroid carcinoma from follicular adenoma. Endocr Pathol 2006, 17:213-223.
• [30]Rossi ED, Raffaelli M, Mule A, Miraglia A, Lombardi CP, Vecchio FM, Fadda G: Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid. Histopathology 2006, 48:795-800.
• [31]Saggiorato E, De Pompa R, Volante M, Cappia S, Arecco F, Dei Tos AP, Orlandi F, Papotti M: 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 2005, 12:305-317.
• [32]Beesley MF, McLaren KM: Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules. Histopathology 2002, 41:236-243.
• [33]Song Q, Wang D, Lou Y, Li C, Fang C, He X, Li J: Diagnostic significance of CK19, TG, Ki67 and galectin-3 expression for papillary thyroid carcinoma in the northeastern region of China. Diagn Pathol 2011, 6:126. BioMed Central Full Text
• [34]Rydlova M, Ludvikova M, Stankova I: Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2008, 152:53-59.
• [35]Raggio E, Camandona M, Solerio D, Martino P, Franchello A, Orlandi F, Gasparri G: The diagnostic accuracy of the immunocytochemical markers in the pre-operative evaluation of follicular thyroid lesions. J Endocrinol Invest 2010, 33:378-381.
• [36]Inohara H, Segawa T, Miyauchi A, Yoshii T, Nakahara S, Raz A, Maeda M, Miyoshi E, Kinoshita N, Yoshida H, et al.: Cytoplasmic and serum galectin-3 in diagnosis of thyroid malignancies. Biochem Biophys Res Commun 2008, 376:605-610.
• [37]Aiad HA, Kandil MA, Asaad NY, El-Kased AM, El-Goday SF: Galectin-3 immunostaining in cytological and histopathological diagnosis of thyroid lesions. J Egypt Natl Canc Inst 2008, 20:36-46.
• [38]Sapio MR, Guerra A, Posca D, Limone PP, Deandrea M, Motta M, Troncone G, Caleo A, Vallefuoco P, Rossi G, et al.: 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 2007, 14:1089-1097.
• [39]Aron M, Kapila K, Verma K: Utility of galectin 3 expression in thyroid aspirates as a diagnostic marker in differentiating benign from malignant thyroid neoplasms. Indian J Pathol Microbiol 2006, 49:376-380.
• [40]Ito Y, Nakamura Y, Yoshida H, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, et al.: Polo-like kinase 1 expression in medullary carcinoma of the thyroid: its relationship with clinicopathological features. Pathobiology 2005, 72:186-190.
• [41]de Matos PS, Ferreira AP, de Oliveira Facuri F, Assumpcao LV, Metze K, Ward LS: Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology 2005, 47:391-401.
• [42]Galusca B, Dumollard JM, Lassandre S, Niveleau A, Prades JM, Estour B, Peoc'h M: Global DNA methylation evaluation: potential complementary marker in differential diagnosis of thyroid neoplasia. Virchows Arch 2005, 447:18-23.
• [43]Nucera C, Mazzon E, Caillou B, Violi MA, Moleti M, Priolo C, Sturniolo G, Puzzolo D, Cavallari V, Trimarchi F, Vermiglio F: Human galectin-3 immunoexpression in thyroid follicular adenomas with cell atypia. J Endocrinol Invest 2005, 28:106-112.
• [44]Weber KB, Shroyer KR, Heinz DE, Nawaz S, Said MS, Haugen BR: The use of a combination of galectin-3 and thyroid peroxidase for the diagnosis and prognosis of thyroid cancer. Am J Clin Pathol 2004, 122:524-531.
• [45]Oestreicher-Kedem Y, Halpern M, Roizman P, Hardy B, Sulkes J, Feinmesser R, Stern Y: Diagnostic value of galectin-3 as a marker for malignancy in follicular patterned thyroid lesions. Head Neck 2004, 26:960-966.
• [46]Volante M, Bozzalla-Cassione F, DePompa R, Saggiorato E, Bartolazzi A, Orlandi F, Papotti M: Galectin-3 and HBME-1 expression in oncocytic cell tumors of the thyroid. Virchows Arch 2004, 445:183-188.
• [47]Torres-Cabala C, Panizo-Santos A, Krutzsch HC, Barazi H, Namba M, Sakaguchi M, Roberts DD, Merino MJ: Differential expression of S100C in thyroid lesions. Int J Surg Pathol 2004, 12:107-115.
• [48]Kovacs RB, Foldes J, Winkler G, Bodo M, Sapi Z: The investigation of galectin-3 in diseases of the thyroid gland. Eur J Endocrinol 2003, 149:449-453.
• [49]Jakubiak-Wielganowicz M, Kubiak R, Sygut J, Pomorski L, Kordek R: Usefulness of galectin-3 immunohistochemistry in differential diagnosis between thyroid follicular carcinoma and follicular adenoma. Pol J Pathol 2003, 54:111-115.
• [50]Giannini R, Faviana P, Cavinato T, Elisei R, Pacini F, Berti P, Fontanini G, Ugolini C, Camacci T, De Ieso K, 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.
• [51]Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW 2nd, Tallini G, Kroll TG, Nikiforov YE: 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.
• [52]Gaffney RL, Carney JA, Sebo TJ, Erickson LA, Volante M, Papotti M, Lloyd RV: Galectin-3 expression in hyalinizing trabecular tumors of the thyroid gland. Am J Surg Pathol 2003, 27:494-498.
• [53]Martins L, Matsuo SE, Ebina KN, Kulcsar MA, Friguglietti CU, Kimura ET: Galectin-3 messenger ribonucleic acid and protein are expressed in benign thyroid tumors. J Clin Endocrinol Metab 2002, 87:4806-4810.
• [54]Coli A, Bigotti G, Zucchetti F, Negro F, Massi G: Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia. Histopathology 2002, 40:80-87.
• [55]Nascimento MC, Bisi H, Alves VA, Longatto-Filho A, Kanamura CT, Medeiros-Neto G: Differential reactivity for galectin-3 in Hurthle cell adenomas and carcinomas. Endocr Pathol 2001, 12:275-279.
• [56]Lavra L, Rinaldo C, Ulivieri A, Luciani E, Fidanza P, Giacomelli L, Bellotti C, Ricci A, Trovato M, Soddu S, et al.: The loss of the p53 activator HIPK2 is responsible for galectin-3 overexpression in well differentiated thyroid carcinomas. PLoS One 2011, 6:e20665.
• [57]Mai KT, Bokhary R, Yazdi HM, Thomas J, Commons AS: Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hurthle cell and/or apocrine-like changes. Histopathology 2002, 40:133-142.
• [58]Ozolins A, Narbuts Z, Strumfa I, Volanska G, Gardovskis J: Diagnostic utility of immunohistochemical panel in various thyroid pathologies. Langenbecks Arch Surg 2010, 395:885-891.
• [59]Liang HS, Zhong YH, Luo ZJ, Huang Y, Lin HD, Luo M, Su HX, Zhou SB, Xie KQ: Comparative analysis of protein expression in differentiated thyroid tumours: a multicentre study. J Int Med Res 2009, 37:927-938.
• [60]Ito Y, Yoshida H, Tomoda C, Miya A, Kobayashi K, Matsuzuka F, Kakudo K, Kuma K, Miyauchi A: 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.
• [61]Mase T, Funahashi H, Koshikawa T, Imai T, Nara Y, Tanaka Y, Nakao A: HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm. Endocr J 2003, 50:173-177.
• [62]Schmitt AC, Cohen C, Siddiqui MT: Paired box gene 8, HBME-1, and cytokeratin 19 expression in preoperative fine-needle aspiration of papillary thyroid carcinoma: diagnostic utility. Cancer Cytopathol 2010, 118:196-202.
• [63]Bonzanini M, Amadori PL, Sagramoso C, Dalla Palma P: Expression of cytokeratin 19 and protein p63 in fine needle aspiration biopsy of papillary thyroid carcinoma. Acta Cytol 2008, 52:541-548.
• [64]Torregrossa L, Faviana P, Filice ME, Materazzi G, Miccoli P, Vitti P, Fontanini G, Melillo RM, Santoro M, Basolo F: CXC chemokine receptor 4 immunodetection in the follicular variant of papillary thyroid carcinoma: comparison to galectin-3 and hector battifora mesothelial cell-1. Thyroid 2010, 20:495-504.
• [65]Pennelli G, Mian C, Pelizzo MR, Naccamulli D, Piotto A, Girelli ME, Mescoli C, Rugge M: Galectin-3 cytotest in thyroid follicular neoplasia: a prospective, monoinstitutional study. Acta Cytol 2009, 53:533-539.
• [66]Franco C, Martinez V, Allamand JP, Medina F, Glasinovic A, Osorio M, Schachter D: Molecular markers in thyroid fine-needle aspiration biopsy: a prospective study. Appl Immunohistochem Mol Morphol 2009, 17:211-215.
• [67]Bartolazzi A, Orlandi F, Saggiorato E, Volante M, Arecco F, Rossetto R, Palestini N, Ghigo E, Papotti M, Bussolati G, et al.: Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study. Lancet Oncol 2008, 9:543-549.
• [68]Carpi A, Naccarato AG, Iervasi G, Nicolini A, Bevilacqua G, Viacava P, Collecchi P, Lavra L, Marchetti C, Sciacchitano S, Bartolazzi A: Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology. Br J Cancer 2006, 95:204-209.
• [69]Kim MJ, Kim HJ, Hong SJ, Shong YK, Gong G: Diagnostic utility of galectin-3 in aspirates of thyroid follicular lesions. Acta Cytol 2006, 50:28-34.
• [70]Collet JF, Hurbain I, Prengel C, Utzmann O, Scetbon F, Bernaudin JF, Fajac A: Galectin-3 immunodetection in follicular thyroid neoplasms: a prospective study on fine-needle aspiration samples. Br J Cancer 2005, 93:1175-1181.
• [71]Maruta J, Hashimoto H, Yamashita H, Noguchi S: Immunostaining of galectin-3 and CD44v6 using fine-needle aspiration for distinguishing follicular carcinoma from adenoma. Diagn Cytopathol 2004, 31:392-396.
• [72]Aratake Y, Umeki K, Kiyoyama K, Hinoura Y, Sato S, Ohno A, Kuribayashi T, Hirai K, Nabeshima K, Kotani T: Diagnostic utility of galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules. Diagn Cytopathol 2002, 26:366-372.
• [73]Bartolazzi A, Gasbarri A, Papotti M, Bussolati G, Lucante T, Khan A, Inohara H, Marandino F, Orlandi F, Nardi F, et al.: Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 2001, 357:1644-1650.
• [74]Rossi ED, Raffaelli M, Minimo C, Mule A, Lombardi CP, Vecchio FM, Fadda G: Immunocytochemical evaluation of thyroid neoplasms on thin-layer smears from fine-needle aspiration biopsies. Cancer 2005, 105:87-95.
• [75]Saggiorato E, Aversa S, Deandreis D, Arecco F, Mussa A, Puligheddu B, Cappia S, Conticello S, Papotti M, Orlandi F: Galectin-3: presurgical marker of thyroid follicular epithelial cell-derived carcinomas. J Endocrinol Invest 2004, 27:311-317.
• [76]Mijovic T, Gologan O, Rochon L, Hier M, Black MJ, Young J, Rivera J, Tamilia M, Payne RJ: Fine-needle aspiration biopsy of the thyroid: review of cytopathologic features predictive of malignancy. J Otolaryngol Head Neck Surg 2009, 38:348-354.
• [77]de Micco C, Savchenko V, Giorgi R, Sebag F, Henry JF: Utility of malignancy markers in fine-needle aspiration cytology of thyroid nodules: comparison of Hector Battifora mesothelial antigen-1, thyroid peroxidase and dipeptidyl aminopeptidase IV. Br J Cancer 2008, 98:818-823.
• [78]Giorgadze T, Rossi ED, Fadda G, Gupta PK, Livolsi VA, Baloch Z: Does the fine-needle aspiration diagnosis of "Hurthle-cell neoplasm/follicular neoplasm with oncocytic features" denote increased risk of malignancy? Diagn Cytopathol 2004, 31:307-312.
• [79]Alaedeen DI, Khiyami A, McHenry CR: Fine-needle aspiration biopsy specimen with a predominance of Hurthle cells: a dilemma in the management of nodular thyroid disease. Surgery 2005, 138:650-656. discussion 656–657
• [80]Eszlinger M, Paschke R: Molecular fine-needle aspiration biopsy diagnosis of thyroid nodules by tumor specific mutations and gene expression patterns. Mol Cell Endocrinol 2010, 322:29-37.
• [81]Kato MA, Fahey TJ 3rd: Molecular markers in thyroid cancer diagnostics. Surg Clin North Am 2009, 89:1139-1155.
• [82]Baloch ZW, Abraham S, Roberts S, LiVolsi VA: Differential expression of cytokeratins in follicular variant of papillary carcinoma: an immunohistochemical study and its diagnostic utility. Hum Pathol 1999, 30:1166-1171.
• [83]Yoshii T, Inohara H, Takenaka Y, Honjo Y, Akahani S, Nomura T, Raz A, Kubo T: Galectin-3 maintains the transformed phenotype of thyroid papillary carcinoma cells. Int J Oncol 2001, 18:787-792.
• [84]Saussez S, Glinoer D, Chantrain G, Pattou F, Carnaille B, Andre S, Gabius HJ, Laurent G: Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid disease. Thyroid 2008, 18:705-712.
• [85]Nga ME, Lim GS, Soh CH, Kumarasinghe MP: HBME-1 and CK19 are highly discriminatory in the cytological diagnosis of papillary thyroid carcinoma. Diagn Cytopathol 2008, 36:550-556.