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Cytokeratin19 expression discriminates papillary thyroid carcinoma from other thyroid lesions and predicts its aggressive behavior

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Abstract

Cytokeratin19 (CK19) has been reported as a useful marker of thyroid tumors. We evaluated its value for differential diagnosis of thyroid neoplastic lesions and assessed its usefulness for predicting aggressive behavior of papillary thyroid carcinomas by correlating immunohistochemical results with clinicopathological features of the patients. A total of 351 thyroid tissue samples included 27 follicular adenomas (FTA), 18 follicular carcinomas (FTC), 147 papillary carcinomas (71 of follicular type-PTCfv and 76 of classical type-PTCcl) and 33 cases of anaplastic carcinoma with 126 adjacent thyroid tissues. Diagnostic usefulness of CK19 was determined by ROC analysis, while its value as a predictive marker of PTC was tested by univariate and multivariate analysis. According to ROC analysis, CK19 can discriminate both types of PTC from other neoplasias of the thyroid gland (p < 0.05). Although greatest accuracy was gained for the identification of PTCcl (91.07 %), this marker was also helpful for distinguishing PTCfv from FTA and FTC (accuracy 71.43 and 65.17 %, respectively). Regarding the univariate set of tests, high expression of CK19 correlated significantly with age, multifocality, extrathyroidal extension, pT status and pTNM stage of PTC (p < 0.05 for all). Multivariate analyses confirmed the significant association of high CK19 expression with extrathyroidal extension of PTC as well as with pTNM stage (p < 0.05 and p < 0.01, respectively). CK19 is a useful marker for the identification of both types of PTC. High expression of this protein predicts the aggressive behavior of PTC and can help in the identification of a particular subgroup of PTC patients with a potentially worse prognosis.

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References

  1. DeLellis RA, Lloyd RY, Heitz PU, Eng C. Pathology and genetics of tumours of endocrine organs. In: DeLellis RA, Lloyd RY, Heitz PU, Eng C, editors. World Health Organization classification of tumors. Lyon: IARC Press, 2004. p. 50–66.

  2. Treseler PA, Clark OH. Prognostic factors in thyroid carcinoma. Surg Oncol Clin N Am. 1997;6(3):555–98.

    PubMed  CAS  Google Scholar 

  3. Brierley JD, Panzarella T, Tsang RW, Gospodarowicz MK, O’Sullivan B. A comparison of different staging systems predictability of patient outcome. Thyroid carcinoma as an example. Cancer. 1997;79(12):2414–23.

    Article  PubMed  CAS  Google Scholar 

  4. Sanders LE, Cady B. Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg. 1998;133(4):419–25.

    Article  PubMed  CAS  Google Scholar 

  5. Dean DS, Hay ID. Prognostic indicators in differentiated thyroid carcinoma. Cancer Control. 2000;7(3):229–39.

    PubMed  CAS  Google Scholar 

  6. Fischer S, Asa SL. Application of immunohistochemistry to thyroid neoplasms. Arch Pathol Lab Med. 2008;132(3):359–72.

    PubMed  Google Scholar 

  7. Serra S, Asa SL. Controversies in thyroid pathology: the diagnosis of follicular neoplasms. Endocr Pathol. 2008;19(3):156–65.

    Article  PubMed  Google Scholar 

  8. Barut F, OnakKandemir 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(2):80–9.

    Article  PubMed  CAS  Google Scholar 

  9. Sethi K, Sarkar S, Das S, Mohanty B, Mandal M. Biomarkers for the diagnosis of thyroid cancer. J Exp Ther Oncol. 2010;8(4):341–52.

    PubMed  CAS  Google Scholar 

  10. Cheng S, Serra S, Mercado M, Ezzat S, Asa SL. A high-throughput proteomic approach provides distinct signatures for thyroid cancer behavior. Clin Cancer Res. 2011;17(8):2385–94.

    Article  PubMed  CAS  Google Scholar 

  11. Bártek J, Bártková J, Taylor-Papadimitriou J, Rejthar A, Kovarík J, Lukás Z, Vojtĕsek B. Differential expression of keratin 19 in normal human epithelial tissues revealed by monospecific monoclonal antibodies. Histochem J. 1986;18(10):565–75.

    Article  PubMed  Google Scholar 

  12. Kwaspen FH, Smedts FM, Broos A, Bulten H, Debie WM, Ramaekers FC. Reproducible and highly sensitive detection of the broad spectrum epithelial marker keratin 19 in routine cancer diagnosis. Histopathology. 1997;31(6):503–16.

    Article  PubMed  CAS  Google Scholar 

  13. Michel M, Török N, Godbout MJ, Lussier M, Gaudreau P, Royal A, Germain L. Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage. J Cell Sci. 1996;109(Pt 5):1017–28.

    PubMed  CAS  Google Scholar 

  14. Jain R, Fischer S, Serra S, Chetty R. The use of Cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. Appl Immunohistochem Mol Morphol. 2010;18(1):9–15.

    Article  PubMed  CAS  Google Scholar 

  15. Sethi K, Sarkar S, Das S, Rajput S, Mazumder A, Roy B, Patra S, Mohanty B, El-Naggar AK, Mandal M. Expressions of CK-19, NF-kappaB, E-cadherin, beta-catenin and EGFR as diagnostic and prognostic markers by immunohistochemical analysis in thyroid carcinoma. J Exp Ther Oncol. 2011;9(3):187–99.

    PubMed  Google Scholar 

  16. Asa SL. The role of immunohistochemical markers in the diagnosis of follicular-patterned lesions of the thyroid. Endocr Pathol. 2005;16(4):295–309.

    Article  PubMed  Google Scholar 

  17. de Matos PS, Ferreira AP, de Oliveira F, Assumpcao LVM, Matze K, Ward LS. Usefulness of HBME-1, Cytokeratin 19 and Galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology. 2005;47:391–401.

    Article  PubMed  Google Scholar 

  18. Park YJ, Kwak SH, Kim DC, Kim H, Choe G, Park do 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(4):621–8.

    Article  PubMed  Google Scholar 

  19. Zhu X, Sun T, Lu H, Zhou X, Lu Y, Cai X, Zhu X. Diagnostic significance of CK19, RET, galectin-3 and HBME-1 expression for papillary thyroid carcinoma. J Clin Pathol. 2010;63(9):786–9.

    Article  PubMed  Google Scholar 

  20. Cheung CC, Ezzat S, Freeman JL, Rosen IB, Asa SL. Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol. 2001;14:338–42.

    Article  PubMed  CAS  Google Scholar 

  21. 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(5):635–6.

    Article  Google Scholar 

  22. Shin E, Chung WY, Yang WI, Park CS, Hong SW. RET/PTC and CK19 expression in papillary thyroid carcinoma and its clinicopathologic correlation. J Korean Med Sci. 2005;20(1):98–104.

    Article  PubMed  CAS  Google Scholar 

  23. Suo Z, Holm R, Nesland JM. Squamous cell carcinomas. An immunohistochemical study of cytokeratins and involucrin in primary and metastatic tumours. Histopathology. 1993;23(1):45–54.

    Article  PubMed  CAS  Google Scholar 

  24. Lam KY, Lo CY, Liu MC. Primary squamous cell carcinoma of the thyroid gland: an entity with aggressive clinical behaviour and distinctive cytokeratin expression profiles. Histopathology. 2001;39(3):279–86.

    Article  PubMed  CAS  Google Scholar 

  25. Rosai J, Carcangiu ML, DeLellis RA. Tumors of the thyroid gland. In: Rosai J, Carcangiu ML, DeLellis RA, editors. Atlas of Tumor Pathology, Third Series, Fascicle 5. Washington, DC: Armed Forces Institute of Pathology; 1992. p. 65–121.

  26. Hermanek P, Sobin LH, editors. UICC: TNM classification of malignant tumors. 4th ed, 2nd revision. Berlin: Springer; 1992.

  27. Laco J, Ryska A, Cáp J, Celakovský P. Expression of galectin-3, cytokeratin 19, neural cell adhesion molecule and E-cadhedrin in certain variants of papillary thyroid carcinoma. Cesk Patol. 2008;44(4):103–7.

    PubMed  CAS  Google Scholar 

  28. Vriens MR, Schreinemakers JM, Suh I, Guerrero MA, Clark OH. Diagnostic markers and prognostic factors in thyroid cancer. Future Oncol. 2009;5(8):1283–93.

    Article  PubMed  CAS  Google Scholar 

  29. Prasad M, Pellegata N, Huang Y, Nagaraja H, de la Chapelle A, Kloos R. Galectin-3, fibronectin-1, CITED-1, HBME-1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid Tumors. Mod Pathol. 2005;18:48–57.

    Article  PubMed  CAS  Google Scholar 

  30. 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. EndocrPathol. 2006;17(3):213–23.

    CAS  Google Scholar 

  31. Uenishi T, Kubo S, Yamamoto T, Shuto T, Ogawa M, Tanaka H, Tanaka S, Kaneda K, Hirohashi K. Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence. Cancer Sci. 2003;94(10):851–7.

    Article  PubMed  CAS  Google Scholar 

  32. Kim H, Choi GH, Na DC, Ahn EY, Kim GI, Lee JE, Cho JY, Yoo JE, Choi JS, Park YN. Human hepatocellular carcinomas with “Stemness”-related marker expression: keratin 19 expression and a poor prognosis. Hepatology. 2011;54(5):1707–17.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Supported by the Ministry of Education and Science of the Republic of Serbia, Project 173050: “molecular characterization of thyroid gland tumors: biological and clinical aspects”. The authors wish to express their gratitude to Dr Anna Nikolic for language correction of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Banatska 31b, 11080, Zemun, Belgrade, Serbia

    Tijana Isic Dencic, Dubravka Cvejic & Svetlana Savin

  2. Center for Endocrine Surgery, Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, 11000, Belgrade, Serbia

    Ivan Paunovic

  3. Institute of Pathology, School of Medicine, University of Belgrade, 11000, Belgrade, Serbia

    Svetislav Tatic & Marija Havelka

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  1. Tijana Isic Dencic
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  2. Dubravka Cvejic
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  3. Ivan Paunovic
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  4. Svetislav Tatic
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  6. Svetlana Savin
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Correspondence to Svetlana Savin.

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Isic Dencic, T., Cvejic, D., Paunovic, I. et al. Cytokeratin19 expression discriminates papillary thyroid carcinoma from other thyroid lesions and predicts its aggressive behavior. Med Oncol 30, 362 (2013). https://doi.org/10.1007/s12032-012-0362-1

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  • DOI: https://doi.org/10.1007/s12032-012-0362-1

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