Skip to main content
SpringerLink
Log in

Prognostic significance of Tiam1 expression in papillary thyroid carcinoma

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

T lymphoma and metastasis gene 1 (Tiam1) is a guanine nucleotide exchange factor (GNEF) that regulates the guanosine triphosphatase to facilitate the exchange of guanosine diphosphate for guanosine triphosphate. It specifically activates Rac1, a member of the Rho family of GTPases. Tiam1 is involved in cell proliferation, cytoskeletal organization, cellular adhesion, and transcriptional activation. It has been suggested that alterations in Tiam1 expression might contribute to the progression of various human cancers. The usefulness of Tiam1 expression as a prognostic marker in papillary thyroid carcinoma (PTC) has not been investigated yet. The aim of this study was to analyze the expression of Tiam1 in PTC as well as its association with the clinicopathologic features and prognostic significance. Surgical tissue samples were taken from 106 PTC patients who had been followed up for at least 9.3 years. Strong expression of Tiam1 was detected in 54% of the cases. Tiam1 expression was associated significantly with various clinicopathologic parameters, such as gender (P = 0.039), tumor multicentricity (P = 0.0124), histologic subtype (P = 0.0427), TNM stage (P = 0.0151), and distant metastases at diagnosis (P = 0.0001). Survival analysis showed that the Tiam1 low-expression group had a significantly shorter overall survival time than Tiam1 high-expression group (P = 0.0007). Multivariate analysis showed that Tiam1 expression was a significant and independent prognostic indicator (P = 0.0090) for PTC patients. Tiam1 expression may be a novel and independent prognostic marker of PTC patients.

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

Similar content being viewed by others

References

  1. Hay ID, Thompson GB, Grant CS, Bergstralh EJ, Dvorak CE, Gorman CA, Maurer MS, Mclver B, Mullan BP, Oberg AL, Powell CC, van Heerden JA, Goellner JR (2002) Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940–1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. World J Surg 26:879–885

    Article  PubMed  Google Scholar 

  2. Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS (1993) Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 114:1050–1057

    PubMed  CAS  Google Scholar 

  3. DeGroot LJ, Kaplan EL, McCormick M, Straus FH (1990) Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab 71:414–424

    Article  PubMed  CAS  Google Scholar 

  4. Shaha AR, Shah JP, Loree TR (1996) Risk group stratification and prognostic factors in papillary carcinoma of thyroid. Ann Surg Oncol 3:534–538

    Article  PubMed  CAS  Google Scholar 

  5. Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States 1973–2002. JAMA 295:2164–2167

    Article  PubMed  CAS  Google Scholar 

  6. Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peoples GE, Devesa SS (2009) Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005. Cancer Epidemiol Biomarkers Prev 18:784–791

    Article  PubMed  Google Scholar 

  7. Habets GG, Scholtes EH, Zuydgeest D, van der Kammen RA, Stam JC, Berns A, Collard JG (1994) Identification of an invasion-inducing gene Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. Cell 77:537–549

    Article  PubMed  CAS  Google Scholar 

  8. Michiels F, Habets GG, Stam JC, van der Kammen RA, Collard JG (1995) A role for Rac in Tiam1-induced membrane ruffling and invasion. Nature 375:338–340

    Article  PubMed  CAS  Google Scholar 

  9. Liu L, Wu DH, Ding YQ (2005) Tiam1 gene expression and its significance in colorectal carcinoma. World J Gastroenterol 11:705–707

    PubMed  CAS  Google Scholar 

  10. Adam L, Vadlamudi RK, McCrea P, Kumar R (2001) Tiam1 overexpression potentiates heregulin-induced lymphoid enhancer factor-1/beta-catenin nuclear signaling in breast cancer cells by modulating the intercellular stability. J Biol Chem 276:28443–28450

    Article  PubMed  CAS  Google Scholar 

  11. Engers R, Mueller M, Walter A, Collard JG, Willers R, Gabbert HE (2006) Prognostic relevance of Tiam1 protein expression in prostate carcinomas. Br J Cancer 95:1081–1086

    Article  PubMed  CAS  Google Scholar 

  12. Ding Y, Chen B, Wang S, Zhao L, Chen J, Ding Y, Chen L, Luo R (2009) Overexpression of Tiam1 in hepatocellular carcinomas predicts poor prognosis of HCC patients. Int J Cancer 124:653–658

    Article  PubMed  CAS  Google Scholar 

  13. Qi Y, Huang B, Yu L, Wang Q, Lan G, Zhang Q (2009) Prognostic value of Tiam1 and Rac1 overexpression in nasopharyngeal carcinoma. ORL J Otorhinolaryngol Relat Spec 71:163–171

    Article  PubMed  CAS  Google Scholar 

  14. Liu H, Shi G, Liu X, Wu H, Fan Q, Wang X (2011) Overexpression of Tiam1 predicts poor prognosis in patients with esophageal squamous cell carcinoma. Oncol Rep 25:841–848

    PubMed  CAS  Google Scholar 

  15. Engers R, Springer E, Michiels F, Collard JG, Gabbert HE (2001) Rac affects invasion of human renal cell carcinomas by up-regulating tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 expression. J Biol Chem 276:41889–41897

    Article  PubMed  CAS  Google Scholar 

  16. Walch A, Seidl S, Hermannstädter C, Rauser S, Deplazes J, Langer R, von Weyhern CH, Sarbia M, Busch R, Feith M, Gillen S, Höfler H, Luber B (2008) Combined analysis of Rac1, IQGAP1, Tiam1 and E-cadherin expression in gastric cancer. Mod Pathol 21:544–552

    Article  PubMed  CAS  Google Scholar 

  17. Wang HX, Xiao XG, Li JH (2007) The expression of Tiam 1 in thyroid carcinoma and its clinical significance. China J Mod Med 17:2437–2440

    CAS  Google Scholar 

  18. Ye YH (2010) Expression of Tiam-1, Flt-4 and CXCR4 in thyroid papillary carcinomas tissues and their clinical significance. Chin J Cancer Prev Treat 17:498–500

    CAS  Google Scholar 

  19. LiVolsi VA, Mazzaferri EL, Schneider AB et al (2004) Papillary carcinoma. In: Delellis RA, Lloyd RV, Heitz PU, Eng C (eds) World Health Organization classification of tumors, pathology and genetics of tumors of endocrine organs. International Agency for Research on Cancer, Lyon, pp 57–66

    Google Scholar 

  20. Sobin LH, Wittekind C (2002) UICC: TNM classification of malignant tumours. Wiley, New York, pp 52–56

    Google Scholar 

  21. Kirkegaard T, Edwards J, Tovey S, McGlynn LM, Krishna SN, Mukherjee R, Tam L, Munro AF, Dunne B, Bartlett JM (2006) Observer variation in immunohistochemical analysis of protein expression, time for a change? Histopathology 48:787–794

    Article  PubMed  CAS  Google Scholar 

  22. Habets GG, van der Kammen RA, Stam JC, Michiels F, Collard JG (1995) Sequence of the human invasion-inducing Tiam1 gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin. Oncogene 10:1371–1376

    PubMed  CAS  Google Scholar 

  23. van Leeuwen FN, van der Kammen RA, Habets GG, Collard JG (1995) Oncogenic activity of Tiam1 and Rac1 in NIH3T3 cells. Oncogene 11:2215–2221

    PubMed  Google Scholar 

  24. Engers R, Zwaka TP, Gohr L, Weber A, Gerharz CD, Gabbert HE (2000) Tiam1 mutations in human renal-cell carcinomas. Int J Cancer 88:369–376

    Article  PubMed  CAS  Google Scholar 

  25. Malliri A, van der Kammen RA, Clark K, van der Valk M, Michiels F, Collard JG (2002) Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature 417:867–871

    Article  PubMed  CAS  Google Scholar 

  26. Minard ME, Kim LS, Price JE, Gallick GE (2004) The role of the guanine nucleotide exchange factor Tiam1 in cellular migration, invasion, adhesion and tumor progression. Breast Cancer Res Treat 84:21–32

    Article  PubMed  CAS  Google Scholar 

  27. Hordijk PL, ten Klooster JP, van der Kammen RA, Michiels F, Oomen LC, Collard JG (1997) Inhibition of invasion of epithelial cells by Tiam1-Rac signaling. Science 278:1464–1466

    Article  PubMed  CAS  Google Scholar 

  28. Malliri A, van Es S, Huveneers S, Collard JG (2004) The Rac exchange factor Tiam1 is required for the establishment and maintenance of cadherin-based adhesions. J Biol Chem 279:30092–30098

    Article  PubMed  CAS  Google Scholar 

  29. Sander EE, ten Klooster JP, van Delft S, van der Kammen RA, Collard JG (1999) Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behaviour. J Cell Biol 147:1009–1021

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the Ministry of Education, Taiwan, ROC (EMRPD1A0391, to CH) and the Chang Gung Medical Research Program (NMRPG376073, to J-DL).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pathology, Chang Gung Memorial Hospital, Linko, Chang Gung University College of Medicine, Kwei-Shan, Taoyuan, Taiwan

    Chuen Hsueh & Shir-Hwa Ueng

  2. Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Chang Gung University College of Medicine, Kwei-Shan, Taoyuan, Taiwan

    Jen-Der Lin & Jui-Hung Sun

  3. Department of Pathology, En Chu Kong Hospital, New Taipei City, Taiwan

    Chia-Fen Yang

  4. Chang Gung Molecular Medicine Research Center and Graduate Institute of Basic Medical Sciences, Chang Gung University College of Medicine, Kwei-Shan, Taoyuan, Taiwan

    Yu-Sun Chang & I-Chin Wu

  5. Department of Surgery, Chang Gung Memorial Hospital, Linko, Chang Gung University College of Medicine, Kwei-Shan, Taoyuan, Taiwan

    Tzu-Chieh Chao

  6. Department of Radiation Oncology, Chang Gung Memorial Hospital, Linko, Chang Gung University College of Medicine, Kwei-Shan, Taoyuan, Taiwan

    Ngan-Ming Tseng

  7. Department of Pathology, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan, 333, Taiwan

    Chuen Hsueh

Authors
  1. Chuen Hsueh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jen-Der Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chia-Fen Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu-Sun Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tzu-Chieh Chao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jui-Hung Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I-Chin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ngan-Ming Tseng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shir-Hwa Ueng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chuen Hsueh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hsueh, C., Lin, JD., Yang, CF. et al. Prognostic significance of Tiam1 expression in papillary thyroid carcinoma. Virchows Arch 459, 587–593 (2011). https://doi.org/10.1007/s00428-011-1164-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-011-1164-0

Keywords

Search

Navigation