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Pathology & Oncology Research

, Volume 16, Issue 1, pp 19–27 | Cite as

High Expression of Claudin-1 Protein in Papillary Thyroid Tumor and its Regional Lymph Node Metastasis

  • Júlia Németh
  • Zsuzsanna Németh
  • Péter Tátrai
  • Ilona Péter
  • Áron Somorácz
  • Attila Marcell Szász
  • András Kiss
  • Zsuzsa SchaffEmail author
Article

Abstract

Claudins, known as major contributors in the formation of the tight junction, are differentially expressed in malignant tumors as compared to the corresponding healthy tissues. Therefore, they are thought to play a role in carcinogenesis and tumor progression. Altered expression of claudin-1 has been reported in several tumor types including endometrial, papillary renal cell and colonic carcinoma, and increased claudin-1 mRNA levels have been observed in papillary thyroid carcinoma (PTC). In this study, we aimed at determining the pattern of claudin-1 expression in various types of thyroid lesions at the protein level and investigating the immunolocalization of β-catenin reported to regulate claudin-1 expression. Samples included 19 PTCs, ten cases of corresponding regional lymph node metastasis, eight papillary microcarcinomas (PMC), 17 follicular thyroid carcinomas (FTC) and 19 follicular adenomas (FA). All cases were evaluated by quantitative immunohistochemistry. Conspicuous claudin-1 immunostaining was detected in the majority of PTC/PMC primary tumors and lymph node metastases (19/27 and 9/10, respectively). On the other hand, we found weak or no claudin-1 expression in any of the FA and FTC cases or peritumoral non-malignant thyroid tissues. Our data prove that high claudin-1 protein expression is specific for PTC and its regional lymph node metastases, while we failed to verify that claudin-1 is regulated by β-catenin in thyroid tumors. Based on these results, claudin-1 may be a useful tumor marker for PTC.

Keywords

Claudin-1 Lymph node metastasis Papillary thyroid carcinoma Tumor marker 

Abbreviations

PTC

Papillary thyroid carcinoma

PMC

Papillary microcarcinoma

FTC

Follicular thyroid carcinoma

FA

Follicular adenoma

HT

Hashimoto’s thyroiditis

TJ

Tight junction

Notes

Acknowledgments

We thank Mrs Magdolna Pekár and Mrs Erzsébet Azumah for preparing the immunohistochemical reactions and Mrs Elvira Rigó Kálé for careful reading and correction of the manuscript. This work was supported by the grant no. 75468 from OTKA (Hungarian Scientific Research Fund).

References

  1. 1.
    Pacini F, Schlumberger M, Dralle H et al (2006) European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 154:787–803CrossRefPubMedGoogle Scholar
  2. 2.
    McNicol A (2007) Pathology of thyroid tumours. Surgery 25:458–462Google Scholar
  3. 3.
    Kondo T, Ezzat S, Asa SL (2006) Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 6:292–306CrossRefPubMedGoogle Scholar
  4. 4.
    DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds) (2004) World Health Organization classification of tumours. Pathology and genetics of tumours of endocrine organs. Thyroid and parathyroid tumours. IARC, Lyon, pp 51–123Google Scholar
  5. 5.
    Patricia SM (2008) Thyroid epithelial tumours. Diagn Histopathol 14:236–246CrossRefGoogle Scholar
  6. 6.
    Arif S, Blanes A, Diaz-Cano SJ (2002) Hashimoto’s thyroiditis shares features with early papillary thyroid carcinoma. Histopathol 41:357–362CrossRefGoogle Scholar
  7. 7.
    Di Pasquale M, Rothstein JL, Palazzo JP (2001) Pathologic features of Hashimoto’s-associated papillary thyroid carcinomas. Hum Pathol 32:24–30CrossRefPubMedGoogle Scholar
  8. 8.
    Repplinger D, Bargren A, Zhang YW et al (2008) Is Hashimoto’s thyroiditis a risk factor for papillary thyroid cancer? J Surg Res 150:49–52CrossRefPubMedGoogle Scholar
  9. 9.
    González-Mariscal L, Betanzos A, Nava P et al (2003) Tight junction proteins. Prog Biophys Mol Biol 81:1–44CrossRefPubMedGoogle Scholar
  10. 10.
    Chiba H, Osanai M, Murata M et al (2008) Transmembrane proteins of tight junctions. Biochim Biophys Acta 1778:588–600CrossRefPubMedGoogle Scholar
  11. 11.
    Furuse M, Fujita K, Hiiragi T et al (1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539–1550CrossRefPubMedGoogle Scholar
  12. 12.
    Hewitt KJ, Agarwal R, Morin PJ (2006) The claudin gene family: expression in normal and neoplastic tissues. BMC Cancer 6:186CrossRefPubMedGoogle Scholar
  13. 13.
    Soini Y (2005) Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathol 46:551–560CrossRefGoogle Scholar
  14. 14.
    Swisshelm K, Macek R, Kubbies M (2005) Role of claudins in tumorigenesis. Adv Drug Deliv Rev 57:919–928 ReviewCrossRefPubMedGoogle Scholar
  15. 15.
    Sobel G, Németh J, Kiss A et al (2006) Claudin 1 differentiates endometrioid and serous papillary endometrial adenocarcinoma. Gynecol Oncol 103:591–598CrossRefPubMedGoogle Scholar
  16. 16.
    Fritzsche FR, Oelrich B, Johannsen M et al (2008) Claudin-1 protein expression is a prognostic marker of patient survival in renal cell carcinomas. Clin Cancer Res 14:7035–7042CrossRefPubMedGoogle Scholar
  17. 17.
    Resnick MB, Konkin T, Routhier J et al (2005) Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study. Mod Pathol 18:511–518CrossRefPubMedGoogle Scholar
  18. 18.
    Borka K, Kaliszky P, Szabó E et al (2007) Claudin expression in pancreatic endocrine tumors as compared with ductal adenocarcinomas. Virchows Arch 450:549–557CrossRefPubMedGoogle Scholar
  19. 19.
    Tőkés AM, Kulka J, Paku S et al (2005) Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Breast Cancer Res 7:R296–R305CrossRefPubMedGoogle Scholar
  20. 20.
    Sobel G, Páska C, Szabó I et al (2005) Increased expression of claudins in cervical squamous intraepithelial neoplasia and invasive carcinoma. Hum Pathol 36:162–169CrossRefPubMedGoogle Scholar
  21. 21.
    Krause G, Winkler L, Mueller SL et al (2008) Structure and function of claudins. Biochim Biophys Acta 1778:631–645PubMedGoogle Scholar
  22. 22.
    Kominsky SL (2006) Claudins: emerging targets for cancer therapy. Expert Rev Mol Med 8:1–11CrossRefPubMedGoogle Scholar
  23. 23.
    Morin PJ (2005) Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 65:9603–9606CrossRefPubMedGoogle Scholar
  24. 24.
    Tzelepi VN, Tsamandas AC, Vlotinou HD et al (2008) Tight junctions in thyroid carcinogenesis: diverse expression of claudin-1, claudin-4, claudin-7 and occludin in thyroid neoplasms. Mod Pathol 21:22–30CrossRefPubMedGoogle Scholar
  25. 25.
    Hucz J, Kowalska M, Jarząb M et al (2006) Gene expression of metalloproteinase 11, claudin 1 and selected adhesion related genes in papillary thyroid cancer. Endokrynol Pol 57(SupplA):18–25PubMedGoogle Scholar
  26. 26.
    Fluge Ø, Bruland O, Akslen LA et al (2006) Gene expression in poorly differentiated papillary thyroid carcinomas. Thyroid 16:161–175CrossRefPubMedGoogle Scholar
  27. 27.
    Miwa N, Furuse M, Tsukita S et al (2001) Involvement of claudin-1 in the β-catenin/Tcf signaling pathway and its frequent pregulation in human colorectal cancers. Oncol Res 12:469–476PubMedGoogle Scholar
  28. 28.
    Halász J, Holczbauer Á, Cs P, Kovács M, Benyó G, Verebély T, Zs S, Kiss A (2006) Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma. Human Pathol 37:555–561CrossRefGoogle Scholar
  29. 29.
    Liu YY, Morreau H, Kievit J et al (2008) 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 158:375–384CrossRefPubMedGoogle Scholar
  30. 30.
    Dhawan P, Singh AB, Deane NG et al (2005) Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. J Clin Invest 115:1765–1776CrossRefPubMedGoogle Scholar
  31. 31.
    Wu YL, Zhang S, Wang GR et al (2008) Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion. World J Gastroenterol 14:4943–4948CrossRefPubMedGoogle Scholar
  32. 32.
    Kondo J, Sato F, Kusumi T et al (2008) Claudin-1 expression is induced by tumor necrosis factor-alpha in human pancreatic cancer cells. Int J Mol Med 22:645–649PubMedGoogle Scholar
  33. 33.
    Chao YC, Pan SH, Yang SC et al (2009) Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma. Am J Respir Crit Care Med 179:123–33CrossRefPubMedGoogle Scholar
  34. 34.
    Aldred MA, Huang Y, Liyanarachchi S et al (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 22:3531–3539CrossRefPubMedGoogle Scholar
  35. 35.
    Firestein R, Bass AJ, Kim SY et al (2008) CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature 455:547–551CrossRefPubMedGoogle Scholar
  36. 36.
    Elzagheid A, Buhmeida A, Korkeila E et al (2008) Nuclear beta-catenin expression as a prognostic factor in advanced colorectal carcinoma. World J Gastroenterol 14:3866–3871CrossRefPubMedGoogle Scholar
  37. 37.
    Ishigaki K, Namba H, Nakashima M et al (2002) Aberrant localization of beta-catenin correlates with overexpression of its target gene in human papillary thyroid cancer. J Clin Endocrinol Metab 87:3433–40CrossRefPubMedGoogle Scholar
  38. 38.
    Wang Z, Qiu S, Eltorky MA et al (2007) Histopathologic and immunohistochemical characterization of a primary papillary thyroid carcinoma in the lateral cervical lymph node. Exp Mol Pathol 82:91–4CrossRefPubMedGoogle Scholar
  39. 39.
    Nikiforov YE (2008) Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol 21(Suppl 2):S37–43CrossRefPubMedGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2009

Authors and Affiliations

  • Júlia Németh
    • 1
  • Zsuzsanna Németh
    • 1
  • Péter Tátrai
    • 1
  • Ilona Péter
    • 2
  • Áron Somorácz
    • 1
  • Attila Marcell Szász
    • 1
  • András Kiss
    • 1
  • Zsuzsa Schaff
    • 1
    Email author
  1. 1.2nd Department of PathologySemmelweis UniversityBudapestHungary
  2. 2.National Institute of OncologyBudapestHungary

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