Skip to main content
SpringerLink
Log in

Expression of intestinal trefoil factor (TFF-3) in hepatocellular carcinoma

  • Research Article
  • Published:
International Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Background: Trefoil peptides (TFF-1, 2, 3) are a family of protease-resistant regulatory factors that play a role in mucosal restitution, angiogenesis, apoptosis, and tumor progression. Intestinal trefoil peptide (TFF-3) expression has been demonstrated in benign hepatobiliary diseases, but there are limited data regarding its expression in HCC.

Methods: Thirty consecutive cases of HCC from 1998 to 2003 were studied. Immunohistochemistry was performed on formalin-fixed paraffin-embedded blocks of HCC using polyclonal antibody to TFF-3. TFF-3 expression was classified as strong, moderate, weak, focal, and negative. Clinical data were obtained per an IRB-approved protocol.

Results: Median age was 69 yr (range: 39–83 yr). Twenty- three patients were males and 7 were females. Treatments included hepatic resection (n=16), chemo-embolization (n=4), combined modality therapy (n=5) and no treatment (n=4). HCC was well differentiated in 12 (40%), moderately differentiated in 13 (43%), and poorly differentiated in 5 (17%) patients. TFF-3 expression was detected in 28/30 (93.3%) patient samples. Sixteen patients (53%) had moderate and 1 (3%) patient had strong TFF-3 expression. Tumor/normal tissue interface was assessable in 21 cases; 11 cases expressed TFF-3 at the interface. There was a strong correlation between tumor grade and TFF-3 expression, wherein poorly differentiated tumors had moderate/strong TFF-3 expression (p=0.008). There was no correlation between TFF-3 expression and survival (p=0.77). Furthermore, there was no correlation among age, disease stage, and survival.

Conclusion: TFF-3 is commonly expressed in HCC and its expression correlates with tumor grade.

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

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, et al. Estimating the world cancer burden: GLOBOCAN 2000. Int J Cancer 2001;94:153–156.

    Article  PubMed  CAS  Google Scholar 

  2. Tanaka Y, Hanada K, Mizokami M, et al. A comparison of the molecular clock of the hepatitis C virus in the United States and Japan predicts that hepatocellular carcinoma in the United States will increase over the next two decades. Proc Natl Acad Sci 2002;99:15,584–15,589.

    CAS  Google Scholar 

  3. Podolysky DK, Lynch-Devaney K, Stow JL, et al. Identification of human intestinal trefoil factor: goblet cell specific expression of a peptide targeted for apical secretion. J Biol Chem 1993;268:6694–6702.

    Google Scholar 

  4. Dignass A, Lynch-Devaney K, Kindon H, et al. Trefoil peptides promote epithelial migration through a transforming growth factor β -independent pathway. J Clin Investig 1994;94:376–383.

    Article  PubMed  CAS  Google Scholar 

  5. Poulsom R, Begos DE, Modlin IM. Molecular aspects of restitution: functions of trefoil peptides. Yale J Biol Med 1996;69:137–146.

    PubMed  CAS  Google Scholar 

  6. Yamachika T, Werther JL, Bodian C, et al. Intestinal Trefoil Factor: A marker of poor prognosis in gastric carcinoma. Clin Cancer Res 2002;8:1092–1099.

    PubMed  CAS  Google Scholar 

  7. Srivastva G, Giraud AS, Ulaganathan M, et al. Biliary epithelial trefoil peptide expression is increased in biliary diseases. Histopathology 2002;40:261–268.

    Article  Google Scholar 

  8. Sasaki M, Tsuneyama K, Saito T, et al. Site-characteristic expression and induction of trefoil factor family 1,2 and 3 and malignant brain tumor-1 in normal and diseased intrahepatic ducts relates to biliary pathophysiology. Liver International 2004;24:29–37.

    Article  PubMed  CAS  Google Scholar 

  9. Sasaki M, Ikeda H, Ohira S, et al. Expression of trefoil factor family 1,2 and 3 peptide is augmented in hepatolithiasis. Peptides 2004; 25:763–770.

    Article  PubMed  CAS  Google Scholar 

  10. Tan D, Li Q, Ramnath N, et al. Prognostic significance of expression of p53 oncoprotein in primary (stage I-IIIa) non-small cell lung cancer. Anticancer Res 2003;23:1665–1672.

    PubMed  CAS  Google Scholar 

  11. CLIP. Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000;31:840–845.

    Article  Google Scholar 

  12. Hoffman W, Jagla W, Wiede A. Molecular medicine of TFF peptides: from gut to brain. Histol Histopathol 2001;16:319–334.

    Google Scholar 

  13. Hoffman W, Jagla W. Cell type specific expression of secretory TFF peptides: colocalization with mucins and synthesis in the brain. Int Rev Cytol 2002;213:147–181.

    Article  Google Scholar 

  14. Jagla W, Wiede A, Dietzmann K, et al. Co-localization of TFF3 peptide and oxytocin in the human hypothalamus. FASEB J 2000;14:1126–1130.

    PubMed  CAS  Google Scholar 

  15. Emami S, Rodrigues S, Rodrigie CM, et al. Trefoil factor family (TFF) peptides and cancer progression. Peptides 2004;25:885–898.

    Article  PubMed  CAS  Google Scholar 

  16. Uchino H, Kataoka H, Itoh H, et al. Expression of intestinal trefoil factor mRNA is downregulated during progression of colorectal carcinoma. J Clin Pathol 1997;50:932–934.

    Article  PubMed  CAS  Google Scholar 

  17. May F, Westley B. Expression of human intestinal trefoil factor in malignant cells and its regulation by oestrogen in breast cancer cells. J Pathol 1997;182:404–413.

    Article  PubMed  CAS  Google Scholar 

  18. Okada H, Kimura MT, Tan D, et al. Frequent trefoil factor 3 (TFF3) overexpression and promoter hypomethylation in mouse and human hepatocellular carcinomas. Int J Oncol 2005;26:369–377.

    PubMed  CAS  Google Scholar 

  19. Efstathiou JA, Noda M, Rowan A, et al. Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in the human colon carcinoma cells. Proc Natl Acad Sci USA 1998;95:3122–3127.

    Article  PubMed  CAS  Google Scholar 

  20. Buschenfelde DM, Hoschutzky H, Tauber R, et al. Molecular mechanisms involved in TFF3 peptide -mediated modulation of the E-cadherin/catenin cell adhesion complex. Peptides 2004;25:873–883.

    Article  Google Scholar 

  21. Liu D, el-Hariry I, Karayiannakis AJ, et al. Phosphorylation of beta-catenin and epidermal growth factor receptor by intestinal trefoil factor. Lab Invest 1997;77:557–563.

    PubMed  CAS  Google Scholar 

  22. Chen YH, Lu Y, De Plaen IG, et al. Transcription factor NF-kappa B signals antianoikic function of trefoil factor 3 on intestinal epithelial cells. Biochem Biophys Res Commun 2000;274:576–582.

    Article  PubMed  CAS  Google Scholar 

  23. Rodrigues S, Van Aken E, Van Bocxlaer S, et al. Trefoil factors as proangiogenic factors in vivo and in vitro: implications of cyclooxygenase-2 and EGF receptor signaling. FASEB J 2003;17:7–16.

    Article  PubMed  CAS  Google Scholar 

  24. Parasole R, Izzo F, Perrone F, et al. Prognostic value of serum biological markers in patients with hepatocellular carcinoma. Clin Cancer Res 2001;7:3504–3509.

    PubMed  CAS  Google Scholar 

  25. Taupin D, Pederson J, Familari M, et al. Augmented intestinal trefoil factor (TFF3) and loss of pS2 expression precedes metaplastic differentiation of gastric epithelium. Lab Invest 2001;81:397–408.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY

    Thaer Khoury, Charles LeVea & Dongfeng Tan

  2. Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY

    Krishdeep Chadha, Milind Javle MD & Renuka Iyer

  3. Department of Biostatistics, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY

    Kathleen Donohue

  4. Department of Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY

    Haruhiko Okada & Hiroki Nagase

Authors
  1. Thaer Khoury
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Krishdeep Chadha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Milind Javle MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kathleen Donohue
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Charles LeVea
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Renuka Iyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Haruhiko Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiroki Nagase
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dongfeng Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Milind Javle MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khoury, T., Chadha, K., Javle, M. et al. Expression of intestinal trefoil factor (TFF-3) in hepatocellular carcinoma. Int J Gastrointest Canc 35, 171–177 (2005). https://doi.org/10.1385/IJGC:35:3:171

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/IJGC:35:3:171

Key Words

Search

Navigation