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Expression pattern of claudins 1 and 3—an auxiliary tool in predicting behavior of mucoepidermoid carcinoma of salivary gland origin

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Abstract

Claudins (CLDNs) are a family of membrane proteins important for permeability of tight junctions. They have also been implicated in carcinogenesis and tumor progression. We analyzed patterns of distribution and intensity of expression of CLDNs 1, 3, 4, and 7 in mucoepidermoid carcinoma (MEC) of salivary gland in 39 patients. Correlations between the expression of CLDNs, tumor grade, and survival were explored. In immunohistochemical analysis, high expression of CLDN 1 was seen in low-grade MEC, and it appeared to be a suitable auxiliary marker of good prognosis. It classified MEC similarly to histological grading in 89.7% of cases (p = 0.001). High CLDN 3 expression was seen in intermediate- and high-grade MEC, while it was low in low-grade MEC. CLDN 3 intensity correctly categorized tumors into grades in 71.8% of cases (p = 0.017). However, in multivariate analysis CLDN 1 and CLDN 3 did not achieve significance over tumor grade in predicting patient behavior. We conclude that analysis of staining intensities of CLDN 1 and 3 is useful as an auxiliary diagnostic and prognostic tool in patients with salivary gland MEC.

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References

  1. Lourenco SV, Coutinho-Camillo CM, Buim MEC et al (2007) Human salivary gland branching morphogenesis: morphological localization of claudins and its parallel relation with developmental stages revealed by expression of cytoskeleton and secretion markers. Histochem Cell Biol 128:361–369

    Article  PubMed  CAS  Google Scholar 

  2. Morin PJ (2005) Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 65:9603–9606

    Article  PubMed  CAS  Google Scholar 

  3. 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 21:22–30

    Article  PubMed  CAS  Google Scholar 

  4. Michikawa H, Fujita-Yoshigaki J, Sugiya H (2008) Enhancement of barrier function by overexpression of claudin-4 in tight junctions of submandibular gland cells. Cell Tissue Res 334:255–264

    Article  PubMed  CAS  Google Scholar 

  5. Tsukita S, Yamazaki Y, Katsuno T et al (2008) Tight junction-based epithelial microenvironment and cell proliferation. Oncogene 27:6930–6938

    Article  PubMed  CAS  Google Scholar 

  6. Peppi M, Ghabriel MN (2004) Tissue-specific expression of the tight junction proteins claudins and occludin in the rat salivary glands. J Anat 205:257–266

    Article  PubMed  CAS  Google Scholar 

  7. Maria OM, Kim J-WM, Gerstenhaber JA et al (2008) Distribution of tight junction proteins in adult human salivary glands. J Histochem Cytochem 56:1093–1098

    Article  PubMed  CAS  Google Scholar 

  8. Singh AB, Sharma A, Dhawan P (2010) Claudin family of proteins and cancer: an overview. J Oncol 2010:541957

    PubMed  Google Scholar 

  9. Miyamoto K, Kusumi T, Kijima H et al (2008) Decreased expression of claudin-1 is correlated with recurrence status in esophageal squamous cell carcinoma. Biomed Res 29:71–76

    Article  PubMed  CAS  Google Scholar 

  10. Pintor dos Reis P, Bharadwaj RR, Kamel-Reid S et al (2008) Claudin 1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma. Cancer 113:3169–3180

    Article  CAS  Google Scholar 

  11. Montgomery E, Mamelak AJ, Berg KD et al (2006) Overexpression of claudin proteins in esophageal adenocarcinoma and its precursor lesions. Appl Immunohistochem Mol Morphol 14:24–30

    Article  PubMed  CAS  Google Scholar 

  12. Al Moustafa A, Alaoui-Jamali MA, Foulkes WD et al (2002) Identification of genes associated with head and neck carcinogenesis by cDNA microarray comparison between matched primary normal epithelial and squamous cells. Oncogene 21:2634–2640

    Article  PubMed  Google Scholar 

  13. Bello IO, Vilen ST, Niinimaa A et al (2008) Expression of claudins 1, 4, 5, and 7 and occludin, and relationship with prognosis in squamous cell carcinoma of the tongue. Hum Pathol 39:1212–1220

    Article  PubMed  CAS  Google Scholar 

  14. Goode RK, Auclair PL, Ellis GL (1998) Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer 82:1217–1224

    Article  PubMed  CAS  Google Scholar 

  15. Luukkaa H, Klemi P, Leivo I et al (2005) Salivary gland cancer in Finland 1991–96: an evaluation of 237 cases. Acta Otolaryngol 125:207–214

    Article  PubMed  Google Scholar 

  16. Brandwein MS, Ivanov K, Mills SE et al (2001) Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading. Am J Surg Pathol 25:835–845

    Article  PubMed  CAS  Google Scholar 

  17. Aro K, Leivo I, Mäkitie AA (2008) Management and outcome of patients with mucoepidermoid carcinoma of major salivary gland origin; a single institution's 30-year experience. Laryngoscope 118:258–262

    Article  PubMed  Google Scholar 

  18. Soini Y (2005) Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology 46:551–560

    Article  PubMed  CAS  Google Scholar 

  19. Soini Y, Tommola S, Helin H et al (2006) Claudin 1, 3, 4 and 5 in gastric carcinoma. Loss of claudin expression associates with the diffuse subtype. Virchows Arch 448:52–58

    Article  PubMed  CAS  Google Scholar 

  20. Soini Y (2004) Claudins 2, 3, 4 and 5 in Paget's disease and breast carcinoma. Hum Pathol 35:1531–1536

    Article  PubMed  CAS  Google Scholar 

  21. Moldway J, Jäckel M, Páska C et al (2007) Distinct claudin expression profile in histologic subtypes of lung cancer. Lung Cancer 57:159–167

    Article  Google Scholar 

  22. Takala H, Saarnio J, Wiik H et al (2007) Claudins 1, 3, 4, 5 and 7 in esophageal cancer: loss of claudin 3 and 4 expression is associated with metastatic behavior. APMIS 115:838–847

    Article  PubMed  CAS  Google Scholar 

  23. 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 14:7035–7042

    Article  PubMed  CAS  Google Scholar 

  24. 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 179:123–133

    Article  PubMed  CAS  Google Scholar 

  25. Sauer T, Pedersen MK, Ebeltoft K et al (2005) Reduced expression of claudin-7 in fine needle aspirates from breast carcinomas correlate with grading and metastatic disease. Cytopathology 16:193–198

    Article  PubMed  CAS  Google Scholar 

  26. Morin PJ (2007) Claudin proteins in ovarian cancer. Dis Markers 23:453–457

    PubMed  CAS  Google Scholar 

  27. Agarwal R, D'Souza T, Morin PJ (2005) Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res 65:7378–7385

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Antti Nevanlinna (MSc) and Professor Seppo Sarna for their expert help in the statistical work. This study was supported by grants from Finnish Cancer Society, Special Government Funding (EVO) of Helsinki, Kuopio and Oulu University Hospitals, Finnish Dental Society Apollonia, Finnish Lung Health Association (Filha), and Maritza and Reino Salonen Foundation.

Disclosure/conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Otolaryngology—Head and Neck Surgery, Helsinki University Central Hospital, Helsinki, Finland

    Katri Aro

  2. Department of Otolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

    Antti A. Mäkitie

  3. Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland

    Luiz Eduardo Blumer Rosa & Ibrahim O. Bello

  4. Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu and Oulu University Hospital, Oulu, Finland

    Tuula Salo

  5. Department of Biosciences and Oral Diagnostic, Oral Pathology, School of Dentistry, UNESP, São José dos Campos, Brazil

    Luiz Eduardo Blumer Rosa

  6. Department of Clinical Pathology and Forensic Medicine, University of Eastern Finland and Department of Pathology, Kuopio University Hospital, Kuopio, Finland

    Ylermi Soini

  7. Haartman Institute, Department of Pathology, University of Helsinki, Helsinki, Finland

    Ibrahim O. Bello

  8. Haartman Institute, Department of Pathology, University of Helsinki and HUSLAB, Helsinki, and Department of Pathology, University of Turku, Turku, Finland

    Ilmo Leivo

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  1. Katri Aro
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  2. Luiz Eduardo Blumer Rosa
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  3. Ibrahim O. Bello
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  4. Ylermi Soini
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  5. Antti A. Mäkitie
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  6. Tuula Salo
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  7. Ilmo Leivo
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Correspondence to Ilmo Leivo.

Additional information

Katri Aro and Luiz Eduardo Blumer Rosa have equal contribution to this study

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Aro, K., Rosa, L.E.B., Bello, I.O. et al. Expression pattern of claudins 1 and 3—an auxiliary tool in predicting behavior of mucoepidermoid carcinoma of salivary gland origin. Virchows Arch 458, 341–348 (2011). https://doi.org/10.1007/s00428-010-1026-1

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  • DOI: https://doi.org/10.1007/s00428-010-1026-1

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