Skip to main content
SpringerLink
Log in

Tumor Protein p53-Induced Nuclear Protein (TP53INP1) Expression in Medullary Thyroid Carcinoma: A Molecular Guide to the Optimal Extent of Surgery?

  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background

Medullary thyroid cancer (MTC) is characterized by early regional lymph node metastasis, the presence of which represents a critical obstacle to cure. At present no molecular markers have been successfully integrated into the clinical care of sporadic MTC. The present study was designed to evaluate TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the optimal extent of surgery performed with curative intent.

Methods

Thirty-eight patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied on embedded paraffin material and on cytological smears.

Results

TP53INP1 was expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was possible to identify two groups of MTC according to the proportion of TP53INP1 expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus 55.5%; P < 0.001). Patients with distant metastases were only observed in group 2. Cytological samples exhibit similar results to their embedded counterparts.

Conclusions

TP53INP1 immunoexpression appears to be a clinical predictor of lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the extent of lymph node dissection in the clinically node-negative neck. These findings require prospective validation.

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

Similar content being viewed by others

References

  1. Dralle H, Scheumann GF, Proye C et al (1995) The value of lymph node dissection in hereditary medullary thyroid carcinoma: a retrospective, European, multicentre study. J Intern Med 238:357–361

    Article  CAS  PubMed  Google Scholar 

  2. Machens A, Hinze R, Thomusch O et al (2002) Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg 26:22–28

    Article  PubMed  Google Scholar 

  3. Machens A, Hofmann C, Hauptmann S et al (2007) Locoregional recurrence and death from medullary thyroid carcinoma in a contemporaneous series: 5-year results. Eur J Endocrinol 157:85–93

    Article  CAS  PubMed  Google Scholar 

  4. Oskam IM, Hoebers F, Balm AJ et al (2008) Neck management in medullary thyroid carcinoma. Eur J Surg Oncol 34:71–76

    CAS  PubMed  Google Scholar 

  5. Hundahl SA, Fleming ID, Fremgen AM et al (1998) A National Cancer Data Base report on 53, 856 cases of thyroid carcinoma treated in the U.S., 1985–1995 (see Comments). Cancer 83:2638–2648

    Article  CAS  PubMed  Google Scholar 

  6. Modigliani E, Cohen R, Campos JM et al (1998) Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’etude des tumeurs a calcitonine. Clin Endocrinol (Oxf) 48:265–273

    Article  CAS  Google Scholar 

  7. Raue F, Kotzerke J, Reinwein D et al (1993) Prognostic factors in medullary thyroid carcinoma: evaluation of 741 patients from the German Medullary Thyroid Carcinoma Register. Clin Invest 71:7–12

    Article  CAS  Google Scholar 

  8. Machens A, Gimm O, Ukkat J et al (2000) Improved prediction of calcitonin normalization in medullary thyroid carcinoma patients by quantitative lymph node analysis. Cancer 88:1909–1915

    Article  CAS  PubMed  Google Scholar 

  9. Scollo C, Baudin E, Travagli JP et al (2003) Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 88:2070–2075

    Article  CAS  PubMed  Google Scholar 

  10. Weber T, Schilling T, Frank-Raue K et al (2001) Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery 130:1044–1049

    Article  CAS  PubMed  Google Scholar 

  11. Ellenhorn JD, Shah JP, Brennan MF (1993) Impact of therapeutic regional lymph node dissection for medullary carcinoma of the thyroid gland. Surgery 114:1078–1081 (discussion 1081–1072)

    CAS  PubMed  Google Scholar 

  12. Fleming JB, Lee JE, Bouvet M et al (1999) Surgical strategy for the treatment of medullary thyroid carcinoma. Ann Surg 230:697–707

    Article  CAS  PubMed  Google Scholar 

  13. Kallinowski F, Buhr HJ, Meybier H et al (1993) Medullary carcinoma of the thyroid—therapeutic strategy derived from fifteen years of experience. Surgery 114:491–496

    CAS  PubMed  Google Scholar 

  14. Kebebew E, Kikuchi S, Duh QY et al (2000) Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer. Arch Surg 135:895–901

    Article  CAS  PubMed  Google Scholar 

  15. Machens A, Holzhausen HJ, Dralle H (2006) Contralateral cervical and mediastinal lymph node metastasis in medullary thyroid cancer: systemic disease? Surgery 139:28–32

    Article  PubMed  Google Scholar 

  16. Moley JF, DeBenedetti MK (1999) Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 229:880–887 (discussion 887–888)

    Article  CAS  PubMed  Google Scholar 

  17. Moley JF, Fialkowski EA (2007) Evidence-based approach to the management of sporadic medullary thyroid carcinoma. World J Surg 31:946–956

    Article  PubMed  Google Scholar 

  18. Kloos RT, Eng C, Evans DB et al (2009) Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19:565–612

    Article  PubMed  Google Scholar 

  19. Iacobone M, Niccoli-Sire P, Sebag F et al (2002) Can sporadic medullary thyroid carcinoma be biochemically predicted? Prospective analysis of 66 operated patients with elevated serum calcitonin levels. World J Surg 26:886–890

    Article  PubMed  Google Scholar 

  20. Niccoli-Sire P, Murat A, Rohmer V et al (2003) When should thyroidectomy be performed in familial medullary thyroid carcinoma gene carriers with non-cysteine RET mutations? Surgery 134:1029–1036 (discussion 1036–1027)

    Article  PubMed  Google Scholar 

  21. Tamagnini P, Iacobone M, Sebag F et al (2005) Lymph node involvement in macroscopic medullary thyroid carcinoma. Br J Surg 92:449–453

    Article  CAS  PubMed  Google Scholar 

  22. Koperek O, Scheuba C, Cherenko M et al (2008) Desmoplasia in medullary thyroid carcinoma: a reliable indicator of metastatic potential. Histopathology 52:623–630

    Article  CAS  PubMed  Google Scholar 

  23. Machens A, Holzhausen HJ, Lautenschlager C et al (2003) Enhancement of lymph node metastasis and distant metastasis of thyroid carcinoma Cancer 98:712–719

    Google Scholar 

  24. Scheuba C, Kaserer K, Kaczirek K et al (2006) Desmoplastic stromal reaction in medullary thyroid cancer—an intraoperative “marker” for lymph node metastases. World J Surg 30:853–859

    Article  PubMed  Google Scholar 

  25. Gironella M, Seux M, Xie MJ et al (2007) Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA 104:16170–16175

    Article  CAS  PubMed  Google Scholar 

  26. Tomasini R, Samir AA, Carrier A et al (2003) TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity. J Biol Chem 278:37722–37729

    Article  CAS  PubMed  Google Scholar 

  27. Tomasini R, Samir AA, Pebusque MJ et al (2002) P53-dependent expression of the stress-induced protein (SIP). Eur J Cell Biol 81:294–301

    Article  CAS  PubMed  Google Scholar 

  28. Tomasini R, Seux M, Nowak J et al (2005) TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity. Oncogene 24:8093–8104

    CAS  PubMed  Google Scholar 

  29. Herfarth KK, Wick MR, Marshall HN et al (1997) Absence of TP53 alterations in pheochromocytomas and medullary thyroid carcinomas. Genes Chromosom Cancer 20:24–29

    Article  CAS  PubMed  Google Scholar 

  30. Chevrier L, Meunier AC, Cochaud S et al (2008) Vasoactive intestinal peptide decreases MYCN expression and synergizes with retinoic acid in a human MYCN-amplified neuroblastoma cell line. Int J Oncol 33:1081–1089

    CAS  PubMed  Google Scholar 

  31. Gommeaux J, Cano C, Garcia S et al (2007) Colitis and colitis-associated cancer are exacerbated in mice deficient for tumor protein 53-induced nuclear protein 1. Mol Cell Biol 27:2215–2228

    Article  CAS  PubMed  Google Scholar 

  32. Jiang PH, Motoo Y, Garcia S et al (2006) Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer. World J Gastroenterol 12:691–696

    CAS  PubMed  Google Scholar 

  33. Jiang PH, Motoo Y, Sawabu N et al (2006) Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells. World J Gastroenterol 12:1597–1602

    CAS  PubMed  Google Scholar 

  34. Machens A, Hauptmann S, Dralle H (2008) Prediction of lateral lymph node metastases in medullary thyroid cancer. Br J Surg 95:586–591

    Article  CAS  PubMed  Google Scholar 

  35. Jiang PH, Motoo Y, Iovanna JL et al (2004) Tumor protein p53-induced nuclear protein 1 (TP53INP1) in spontaneous chronic pancreatitis in the WBN/Kob rat: drug effects on its expression in the pancreas. JOP 5:205–216

    PubMed  Google Scholar 

  36. Ito Y, Motoo Y, Yoshida H et al (2006) Decreased expression of tumor protein p53-induced nuclear protein 1 (TP53INP1) in breast carcinoma. Anticancer Res 26:4391–4395

    CAS  PubMed  Google Scholar 

  37. Ito Y, Motoo Y, Yoshida H et al (2006) High level of tumour protein p53-induced nuclear protein 1 (TP53INP1) expression in anaplastic carcinoma of the thyroid. Pathology 38:545–547

    Article  CAS  PubMed  Google Scholar 

  38. Nikiforova MN, Tseng GC, Steward D et al (2008) MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab 93:1600–1608

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM).

Author information

Authors and Affiliations

  1. INSERM U624 “Stress Cellulaire”, Parc Scientifique et Technologique de Luminy, Case 915, 13288, Marseille, France

    D. Taïeb, S. Giusiano, N. J. Dusetti, J. L. Iovanna, S. Garcia & Colette Taranger-Charpin

  2. Service d’Anatomopathologie, Centre Hospitalo-universitaire Nord, Chemin des Bourrelly, 13915, Marseille, France

    S. Giusiano, M. Marcy, C. de Micco, S. Garcia & Colette Taranger-Charpin

  3. Service de Chirurgie Générale et Endocrinienne de la Timone, 264 rue Saint-Pierre, 13385, Marseille, France

    F. Sebag, F. F. Palazzo & J. F. Henry

Authors
  1. D. Taïeb
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Giusiano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Sebag
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Marcy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. de Micco
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. F. Palazzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N. J. Dusetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. L. Iovanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. F. Henry
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S. Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Colette Taranger-Charpin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Garcia.

Additional information

D. Taïeb and S. Giusiano contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taïeb, D., Giusiano, S., Sebag, F. et al. Tumor Protein p53-Induced Nuclear Protein (TP53INP1) Expression in Medullary Thyroid Carcinoma: A Molecular Guide to the Optimal Extent of Surgery?. World J Surg 34, 830–835 (2010). https://doi.org/10.1007/s00268-010-0395-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-010-0395-6

Keywords

Search

Navigation