Skip to main content

Advertisement

SpringerLink
Log in

Increased immunoexpression of trefoil factors in salivary gland tumors

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objective

Very little is known about the role of trefoil factors (TFFs) in salivary gland tumors, and TFF immunoexpression has never been investigated in such tumors. The aim of this study was to evaluate TFF immunoexpression in benign and malignant salivary gland tumors.

Materials and methods

Benign (n = 25) and malignant (n = 25) salivary gland tumor specimens were included in this study, using mucocele (n = 25) specimens as a control group. Immunohistochemical staining was performed to evaluate the expression of TFFs (TFF1, TFF2, and TFF3) by semiquantitative means.

Results

Expression of TFF1, TFF2, and TFF3 was significantly increased in benign (p = 0.001, p = 0.005, p < 0.001, respectively) and malignant (p < 0.001, p < 0.001, p < 0.001, respectively) groups as compared with the control group. Patterns of co-expression between TFF1/TFF2, TFF2/TFF3, and TFF1/TFF3 were different among the three groups.

Conclusions

The present study provided new information showing that all TFFs were significantly increased in benign and malignant salivary gland tumors, and overexpression of TFFs could be associated with neoplastic transformation in salivary gland tissues.

Clinical relevance

Overexpression of TFFs may be useful as biomarkers in terms of differential diagnosis between salivary gland tumors and other oral neoplasms for which clinical manifestations are indistinguishable.

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

Similar content being viewed by others

References

  1. Kjellev S (2009) The trefoil factor family—small peptides with multiple functionalities. Cell Mol Life Sci 66:1350–1369

    Article  PubMed  Google Scholar 

  2. Thim L, May FEB (2005) Structure of mammalian trefoil factors and functional insights. Cell Mol Life Sci 62:2956–2973

    Article  PubMed  Google Scholar 

  3. Madsen J, Nielsen O, Tornøe I, Thim L, Holmskov U (2007) Tissue localization of human trefoil factors 1, 2, and 3. J Histochem Cytochem 55:505–513

    Article  PubMed  Google Scholar 

  4. Samson MH, Chaiyarit P, Nortvig H, Vestergaad EM, Ernst E, Nexø E (2011) Trefoil factor family peptides in human saliva and in cyclical cervical mucus. Method evaluation and results on healthy individuals. Clin Chem Lab Med 49:861–868

    PubMed  Google Scholar 

  5. Jagla W, Wiede A, Hinz M, Dietzmann K, Gülicher D, Gerlach KL, Hoffmann W (1999) Secretion of TFF-peptides by human salivary glands. Cell Tissue Res 298:161–166

    Article  PubMed  Google Scholar 

  6. Devine DA, High AS, Owen PJ, Poulsom R, Bonass WA (2000) Trefoil factor expression in normal and diseased human salivary glands. Hum Pathol 31:509–515

    Article  PubMed  Google Scholar 

  7. Kouznetsova I, Gerlach KL, Zahl C, Hoffmann W (2010) Expression analysis of human salivary glands by laser microdissection: differences between submandibular and labial glands. Cell Physiol Biochem 26:375–382

    Article  PubMed  Google Scholar 

  8. Kutta H, May J, Jaehne M, Münscher A, Paulsen FP (2006) Antimicrobial defence mechanisms of the human parotid duct. J Anat 208:609–619

    Article  PubMed Central  PubMed  Google Scholar 

  9. Storesund T, Schreurs O, Messelt EB, Kolltveit KM, Schenck K (2009) Trefoil factor family 3 expression in the oral cavity. Eur J Oral Sci 117:636–643

    Article  PubMed  Google Scholar 

  10. Chaiyarit P, Chayasadom A, Wara-Aswapati N, Hormdee D, Sittisomwong S, Nakaresisoon S, Samson MH, Pitiphat W, Giraud AS (2012) Trefoil factors in saliva and gingival tissues of patients with chronic periodontitis. J Periodontol 83:1129–1138

    Article  PubMed  Google Scholar 

  11. Storesund T, Hayashi K, Kolltveit KM, Bryne M, Schenck K (2008) Salivary trefoil factor 3 enhances migration of oral keratinocytes. Eur J Oral Sci 116:135–140

    Article  PubMed  Google Scholar 

  12. Storesund T, Schenck K, Osmundsen H, Røed A, Helgeland K, Kolltveit KM (2009) Signal transduction and gene transcription induced by TFF3 in oral keratinocytes. Eur J Oral Sci 117:511–517

    Article  PubMed  Google Scholar 

  13. Perry JK, Kannan N, Grandison PM, Mitchell MD, Lobie PE (2008) Are trefoil factors oncogenic? Trends Endocrinol Metab 19:74–81

    Article  PubMed  Google Scholar 

  14. Emami S, Rodrigues S, Rodrigue CM, Le Floch N, Rivat C, Attoub S, Bruyneel E, Gespach C (2004) Trefoil factor family (TFF) peptides and cancer progression. Peptides 25:885–898

    Article  PubMed  Google Scholar 

  15. Buache E, Etique N, Alpy F, Stoll I, Muckensturm M, Reina-San-Martin B, Chenard MP, Tomasetto C, Rio MC (2011) Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice. Oncogene 30:3261–3273

    Article  PubMed Central  PubMed  Google Scholar 

  16. Yio X, Zhang JY, Babyatsky M, Chen A, Lin J, Fan QX, Werther JL, Itzkowitz S (2005) Trefoil factor family-3 is associated with aggressive behavior of colon cancer cells. Clin Exp Metastasis 22:157–165

    Article  PubMed  Google Scholar 

  17. Vestergaard EM, Nexø E, Tørring N, Borre M, Ørntoft TF, Sørensen KD (2010) Promoter hypomethylation and upregulation of trefoil factors in prostate cancer. Int J Cancer 127:1857–1865

    Article  PubMed  Google Scholar 

  18. Chaiyarit P, Utrawichian A, Leelayuwat C, Vatanasapt P, Chanchareonsook N, Samson MH, Giraud AS (2012) Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma. Clin Oral Invest 16:1549–1556

    Article  Google Scholar 

  19. Eveson JW (2011) Salivary tumours. Periodontology 2000(57):150–159

    Article  Google Scholar 

  20. Auclair PL, Ellis GL, Gnepp DR, Wenig BM, Janney CG (1991) Salivary gland neoplasms: general considerations. In: Ellis GL, Auclair PL, Gnepp DR (eds) Surgical pathology of the salivary glands. Saunders, Philadelphia, pp 135–164

    Google Scholar 

  21. Camelo-Piragua SI, Habib C, Kanumuri P, Lago CE, Mason HS, Otis CN (2009) Mucoepidermoid carcinoma of the breast shares cytogenetic abnormality with mucoepidermoid carcinoma of the salivary gland: a case report with molecular analysis and review of the literature. Hum Pathol 40:887–892

    Article  PubMed  Google Scholar 

  22. Flynn C, Kadivar M, Kwon MY, Bonzanini M, Haines GK III, Tavassoli FA (2012) Basal cell adenocarcinoma arsing in salivary gland metaplasia of the breast: a novel salivary gland-type tumor developing in the breast. Hum Pathol 43:1764–1771

    Article  PubMed  Google Scholar 

  23. Marchio C, Weigelt B, Reis-Filho JS (2010) Adenoid cystic carcinomas of the breast and salivary glands (or ‘The strange case of Dr Jekyll and Mr Hyde’ of exocrine gland carcinomas). J Clin Pathol 63:220–228

    Article  PubMed  Google Scholar 

  24. Smid M, Wang Y, Klijn JG, Sieuwerts AM, Zhang Y, Atkins D, Martens JW, Foekens JA (2006) Genes associated with breast cancer metastatic to bone. J Clin Oncol 24:2261–2267

    Article  PubMed  Google Scholar 

  25. Bosma AJ, Weigelt B, Lambrechts AC, Verhagen OJ, Pruntel R, Hart AA, Rodenhuis S, van't Veer LJD (2002) Detection of circulating breast tumor cells by differential expression of marker genes. Clin Cancer Res 8:1871–1877

    PubMed  Google Scholar 

  26. Lacroix M (2006) Significance, detection and markers of disseminated breast cancer cells. Endocr Relat Cancer 13:1033–1067

    Article  PubMed  Google Scholar 

  27. Eveson JW (2005) WHO histological classification of tumours of the salivary glands. In: Barnes L, Eveson JW, Reichart P, Sidransky D (eds) World Health Organization classification of tumours: pathology and genetics of head and neck tumours. IARC, Lyon, p 210

    Google Scholar 

  28. Walker RA (2006) Quantification of immunohistochemistry: issues concerning methods, utility and semiquantitative assessment I. Histopathology 49:406–410

    Article  PubMed  Google Scholar 

  29. Srivatsa G, Giraud AS, Ulaganathan M, Yeomans ND, Dow C, Nicoll AJ (2002) Biliary epithelial trefoil peptide expression is increased in biliary diseases. Histopathology 40:261–268

    Article  PubMed  Google Scholar 

  30. Taupin D, Pedersen J, Familari M, Cook G, Yeomans N, Giraud AS (2001) Augmented intestinal trefoil factor (TFF3) and loss of pS2 (TFF1) expression precedes metaplastic differentiation of gastric epithelium. Lab Invest 81:397–408

    Article  PubMed  Google Scholar 

  31. Taupin DR, Pang KC, Green SP, Giraud AS (1995) The trefoil peptides spasmolytic polypeptide and intestinal trefoil factor are major secretory products of the rat gut. Peptides 6:1001–1005

    Article  Google Scholar 

  32. Poulsom R, Hanby AM, Lalani EN, Hauser F, Hoffmann W, Stamp GW (1997) Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co-expressed in normal, hyperplastic, and neoplastic human breast epithelium. J Pathol 183:30–38

    Article  PubMed  Google Scholar 

  33. Regalo G, Wright NA, Machado JC (2005) Trefoil factors: from ulceration to neoplasia. Cell Mol Life Sci 62:2910–2915

    Article  PubMed  Google Scholar 

  34. Dhar DK, Wang TC, Tabara H, Tonomoto Y, Maruyama R, Tachibana M, Kubota H, Nagasue N (2005) Expression of trefoil factor family members correlates with patient prognosis and neoangiogenesis. Clin Cancer Res 11:6472–6478

    Article  PubMed  Google Scholar 

  35. Welter C, Theisinger B, Rio MC, Seitz G, Schüder G, Blin N (1994) Expression pattern of breast-cancer-associated protein pS2/BCEI in colorectal tumors. Int J Cancer 56:52–55

    Article  PubMed  Google Scholar 

  36. Luo J, Duggan DJ, Chen Y, Sauvageot J, Ewing CM, Bittner ML, Trent JM, Isaacs WB (2001) Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling. Cancer Res 61:4683–4688

    PubMed  Google Scholar 

  37. Peterson A, Menheniott TR, O'Connor LO, Walduck AK, Fox JG, Kawakami K, Minamoto T, Ong EK, Wang TC, Judd LM, Giraud AS (2010) Helicobacter pylori infection methylates and silences TFF2 leading to gastric tumor development in mice and humans. Gastroenterology 139:2005–2017

    Article  PubMed Central  PubMed  Google Scholar 

  38. Tomita H, Takaishi S, Menheniott TR, Yang X, Shibata W, Betz KS, Kawakami K, Minamoto T, Tomasetto C, Rio MC, Giraud AS, Wang TC (2011) Hormonal inhibition of gastric carcinogenesis is mediated by suppression of epigenetic silencing of TFF1. Gastroenterology 140:879–891

    Article  PubMed Central  PubMed  Google Scholar 

  39. Dossinger V, Kayademir T, Blin N, Gött P (2002) Down-regulation of TFF expression in gastrointestinal cell lines by cytokines and nuclear factors. Cell Physiol Biochem 12:197–206

    Article  PubMed  Google Scholar 

  40. Amiry N, Kong X, Muniraj N, Kannan N, Grandison PM, Lin J, Yang Y, Vouyovitch CM, Borges S, Perry JK, Mertani HC, Zhu T, Liu D, Lobie PE (2009) Trefoil factor-1 (TFF1) enhances oncogenicity of mammary carcinoma cells. Endocrinology 150:4473–4483

    Article  PubMed  Google Scholar 

  41. Kannan N, Kang J, Kong X, Tang J, Perry JK, Mohankumar KM, Miller LD, Liu ET, Mertani HC, Zhu T, Grandison PM, Liu DX, Lobie PE (2010) Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Neoplasia 12:1041–1053

    PubMed Central  PubMed  Google Scholar 

  42. Siu LS, Romanska H, Abel PD, Baus-Loncar M, Kayademir T, Stamp GW, Lalani el N (2004) TFF2 (trefoil family factor2) inhibits apoptosis in breast and colorectal cancer cell lines. Peptides 25:855–863

    Article  PubMed  Google Scholar 

  43. May FE, Semple JI, Prest SJ, Westley BR (2004) Expression and motogenic activity of TFF2 in human breast cancer cells. Peptides 25:865–872

    Article  PubMed  Google Scholar 

  44. Samson MH (2013) Quantitative measurements of trefoil factor family peptides: possibilities and pitfalls. Scand J Clin Lab Invest. doi: 10.3109/00365513.2013.765962

Download references

Acknowledgments

This research work was supported by Khon Kaen University and the National Health and Medical Research Council, Australia.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Oral Diagnosis, Faculty of Dentistry, Khon Kaen University, Khon Kaen, 40002, Thailand

    Ponlatham Chaiyarit, Poramaporn Klanrit, Pensri Photipakdee & Ajiravudh Subarnbhesaj

  2. Research group of chronic inflammatory oral diseases and systemic diseases associated with oral health, Khon Kaen University, Khon Kaen, 40002, Thailand

    Ponlatham Chaiyarit, Poramaporn Klanrit, Pensri Photipakdee & Ajiravudh Subarnbhesaj

  3. Murdoch Childrens Research Institute, The Royal Children’s Hospital, Flemington Road Parkville, Melbourne, VIC, 3052, Australia

    Andrew S. Giraud

Authors
  1. Ponlatham Chaiyarit
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Poramaporn Klanrit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pensri Photipakdee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ajiravudh Subarnbhesaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew S. Giraud
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ponlatham Chaiyarit.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chaiyarit, P., Klanrit, P., Photipakdee, P. et al. Increased immunoexpression of trefoil factors in salivary gland tumors. Clin Oral Invest 18, 1305–1312 (2014). https://doi.org/10.1007/s00784-013-1094-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-013-1094-0

Keywords

Search

Navigation