Skip to main content

Advertisement

SpringerLink
Log in

Universal Markers of Thyroid Malignancies: Galectin-3, HBME-1, and Cytokeratin-19

  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Difficulties in diagnosis of thyroid lesions, even with histologic analysis, are well known. This study has been carried on to evaluate the role of immunohistochemical markers including galectin-3, Hector Battifora mesothelial cell-1 (HBME-1), and cytokeratin-19 in the diagnosis and differential diagnosis of benign and malignant thyroid lesions. The expressions of galectin-3, HBME-1, and cytokeratin-19 were tested in formalin-fixed, paraffin-embedded tissues from 458 surgically resected thyroid lesions including non-neoplastic and neoplastic lesions. Immunostaining with standard avidin–biotin complex technique was performed by using monoclonal antibodies. In malignant neoplastic thyroid lesions, galectin-3, HBME-1, and cytokeratin-19 were diffusely expressed in general. Diffuse expression rates of these three markers were 72.3% (47/65), 70.7% (46/65), and 76.9% (50/65), respectively. The use of galectin-3, HBME-1, and cytokeratin-19 may provide significant contributions in the differential diagnosis of malignant thyroid tumors. Although focal galectin-3, HBME-1, and cytokeratin-19 expression may be encountered in benign lesions, diffuse positive reactions for these three markers are characteristic of malignant lesions. It has concluded that cytokeratin-19 alone and its combinations with other markers were more sensitive in accurate diagnosis of papillary carcinoma than the other combinations; meanwhile, there were similar results for follicular carcinomas with HBME-1 alone and its combinations.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Schelfhout LJ, Van Muijen GN, Fleuren GJ. Expression of keratin 19 distinguishes papillary thyroid carcinoma from follicular carcinomas and follicular thyroid adenoma. Am J Clin Pathol 92:654–8, 1989.

    CAS  PubMed  Google Scholar 

  2. Weber KB, Shroyer KR, Heinz DE, Nawaz S, Said S, 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 122:524–31, 2004.

    Article  PubMed  Google Scholar 

  3. Park YJ, Kwak SH, Kim DC, Kim H, Choe G, Park do J, et al. 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 22:621–8, 2007.

    Article  PubMed  Google Scholar 

  4. El Demellawy D, Nasr A, Alowami S. Application of CD56, P63 and CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid. Diagn Pathol 3:5, 2008.

    Article  PubMed  Google Scholar 

  5. Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, de la Chapelle A, Kloos RT. Galectin-3, fibronectin-1, CITED-1, HBME-1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 18:48–57, 2005.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Türköz HK, Oksüz H, Yurdakul Z, Ozcan D. Galectin-3 expression in tumor progression and metastasis of papillary thyroid carcinoma. Endocr Pathol 19:92–6, 2008.

    Article  PubMed  Google Scholar 

  8. de Matos PS, Ferreira AP, de Oliveira Facuri F, Assumpção LV, Metze K, Ward LS. Usefulness of HBME-1, cytokeratin-19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology 47:391–401, 2005.

    Article  PubMed  Google Scholar 

  9. Beesley MF, McLaren KM. Cytokeratin-19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules. Histopathology 41:236–43, 2002.

    Article  CAS  PubMed  Google Scholar 

  10. Choi YL, Kim MK, Suh JW, Han J, Kim JH, Yang JH, et al. Immunoexpression of HBME-1, high molecular weight cytokeratin, cytokeratin-19, thyroid transcription factor-1, and E-cadherin in thyroid carcinomas. J Korean Med Sci 20:853–9, 2005.

    Article  CAS  PubMed  Google Scholar 

  11. Wiseman SM, Melck A, Masoudi H, Ghaidi F, Goldstein L, Gown A, et al. Molecular phenotyping of thyroid tumors identifies a marker panel for differentiated thyroid cancer diagnosis. Ann Surg Oncol 15:2811–26, 2008.

    Article  PubMed  Google Scholar 

  12. 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 17:225–34, 2006.

    Article  CAS  PubMed  Google Scholar 

  13. Papotti M, Rodriguez J, De Pompa 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 18:541–6, 2005.

    Article  CAS  PubMed  Google Scholar 

  14. Orlandi F, Saggiorato E, Pivano G, Puligheddu B, Termine A, Cappia S, et al. Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer Res 58:3015–20, 1998.

    CAS  PubMed  Google Scholar 

  15. Inohara H, Honjo Y, Yoshii T, Akahani S, Yoshida J, Hattori K, et al. Expression of galectin-3 in fine-needle aspirates as a diagnostic marker differentiating benign from malignant thyroid neoplasms. Cancer 85:2475–84, 1999.

    Article  CAS  PubMed  Google Scholar 

  16. Kawachi K, Matsushita Y, Yonezawa S, Nakano S, Shirao K, Natsugoe S, et al. Galectin-3 expression in various thyroid neoplasms and its possible role in metastasis formation. Hum Pathol 31:428–33, 2000.

    Article  CAS  PubMed  Google Scholar 

  17. Bartolazzi A, Gasbarri A, Papotti M, Bussolati G, Lucante T, Khan A, et al. and the Thyroid Cancer Study Group. Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644–50, 2001.

    Article  CAS  PubMed  Google Scholar 

  18. Bernet VJ, Anderson J, Vaishnav Y, Solomon B, Adair CF, Saji M, 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 87:4792–6, 2002.

    Article  CAS  PubMed  Google Scholar 

  19. Kovàcs RB, Földes J, Winkler G, Bodò M, Sàpi Z. The investigation of galectin-3 in diseases of thyroid gland. Eur J Endocrinol 149:449–53, 2003.

    Article  PubMed  Google Scholar 

  20. Volante M, Bozzalla-Cassione F, Orlandi F, Papotti M. Diagnostic role of galectin-3 in follicular thyroid tumors. Virchows Arch 444:309–12, 2004.

    Article  PubMed  Google Scholar 

  21. Than TH, Swethadri GK, Wong J, Ahmad T, Jamil D, Maganlal RK, et al. Expression of galectin-3 and galectin-7 in thyroid malignancy as potential diagnostic indicators. Singapore Med J 49:333–8, 2008.

    CAS  PubMed  Google Scholar 

  22. Oestreicher-Kedem Y, Halpern M, Roizman P, Hardy B, Sulkes J, Feinmesser R, et al. Diagnostic value of galectin-3 as a marker for malignancy in follicular patterned thyroid lesions. Head Neck 26:960–6, 2004.

    Article  PubMed  Google Scholar 

  23. Ito Y, Yoshida H, Tomoda C, Miya A, Kobayashi K, Matsuzuka F, et al. Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma. Pathology 37:296–8, 2005.

    Article  CAS  PubMed  Google Scholar 

  24. Cvejic D, Savin S, Petrovic I, Paunovic I, Tatic S, Krgovic K, et al. Galectin-3 expression in papillary microcarcinoma of the thyroid. Histopathology 47:209–14, 2005.

    Article  CAS  PubMed  Google Scholar 

  25. Rossi ED, Raffaelli M, Minimo C, Mule A, Lombardi CP, Vecchio FM, et al. Immunocytochemical evaluation of thyroid neoplasms on thin-layer smears from fine-needle aspiration biopsies. Cancer 105:87–95, 2005.

    Article  PubMed  Google Scholar 

  26. Saggiorato E, De Pompa R, Volante M, Cappia S, Arecco F, Dei Tos AP, et al. 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 12:305–17, 2005.

    Article  CAS  PubMed  Google Scholar 

  27. Castro R, Gharib H. Continuing controversies in the management of thyroid nodules. Ann Intern Med 142:926–31, 2005.

    PubMed  Google Scholar 

  28. Prasad ML, Huang Y, Pellegata NS, de la Chapelle A, Kloos RT. Hashimoto’s thyroiditis with papillary thyroid carcinoma (PTC) - like nuclear alterations expresses molecular markers of PTC. Histopathology 45:39–46, 2004.

    Article  CAS  PubMed  Google Scholar 

  29. Erkiliç S, Aydin A, Koçer NE. Diagnostic utility of cytokeratin 19 expression in multinodular goiter with papillary areas and papillary carcinoma of thyroid. Endocr Pathol 13:207–11, 2002.

    Article  PubMed  Google Scholar 

  30. Fonseca E, Nesland JM, Höie J, Sobrinho-Simões M. Pattern of expression of intermediate cytokeratin filaments in the thyroid gland: an immunohistochemical study of simple and stratified epithelial-type cytokeratins. Virchows Arch 430:239–45, 1997.

    Article  CAS  PubMed  Google Scholar 

  31. DeLellis RA, Williams ED. Thyroid and parathyroid tumours: introduction. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, editors. World health organization classification of tumours. Pathology and genetics of tumours of endocrine organs. Lyon: IARC Press; 2004.

    Google Scholar 

  32. Rossi ED, Raffaelli M, Mule’ A, Miraglia A, Lombardi CP, Vecchio FM, et al. Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid. Histopathology 48:795–800, 2006.

    Article  CAS  PubMed  Google Scholar 

  33. 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 126:700–8, 2006.

    Article  CAS  PubMed  Google Scholar 

  34. Mase T, Funahashi H, Koshikawa T, Imai T, Nara Y, Tanaka Y, et al. HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm. Endocr J 50:173–7, 2003.

    Article  PubMed  Google Scholar 

  35. 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 19:1631–7, 2006.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Zonguldak Karaelmas University Faculty of Medicine, 67600, Kozlu, Zonguldak, Turkey

    Figen Barut, Nilufer Onak Kandemir, Sibel Bektas, Burak Bahadir & Sukru Oguz Ozdamar

  2. Department of Pathology, Lutfi Kırdar Kartal Training and Research Hospital, Istanbul, Turkey

    Sevinc Keser

Authors
  1. Figen Barut
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nilufer Onak Kandemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sibel Bektas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Burak Bahadir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sevinc Keser
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sukru Oguz Ozdamar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Figen Barut.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barut, F., Onak Kandemir, N., Bektas, S. et al. Universal Markers of Thyroid Malignancies: Galectin-3, HBME-1, and Cytokeratin-19. Endocr Pathol 21, 80–89 (2010). https://doi.org/10.1007/s12022-010-9114-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12022-010-9114-y

Keywords

Search

Navigation