Advertisement

World Journal of Surgery

, 32:2617 | Cite as

Clinical Significance of P53 Protein Expression in Papillary Thyroid Carcinoma

  • Naomi Morita
  • Yoshifumi Ikeda
  • Hiroshi Takami
Article

Abstract

Background

Although mutations in the p53 suppressor gene in thyroid carcinoma have usually been detected in anaplastic carcinoma, P53 protein expression has been detected immunohistochemically in papillary thyroid carcinoma (PTC). In the present study, we examined the immunohistochemical expression of P53 protein in PTC to investigate the relations between its expression and the clinicopathologic features.

Methods

The study was performed on 68 patients in whom thyroidectomy with lymph node dissection had been performed to treat PTC at Teikyo University Hospital. Expression of P53 protein was evaluated immunohistochemically in sections of paraffin-embedded tissue in 68 primary tumors and 196 lymph node metastases.

Results

Overexpression of P53 protein in the primary tumor was observed in 29 cases (43%). Statistical analysis revealed significant correlation between P53 protein expression in the primary tumor and large tumor size (unpaired t-test: p < 0.01), the presence of lymph node metastasis (unpaired t-test: p < 0.05), and the mean number of lymph node metastases (unpaired t-test: p < 0.05). Although 29 (43%) of the primary tumors overexpressed P53 protein, 143 (73%) of the metastatic lymph nodes overexpressed P53 protein irrespective of whether there was P53 overexpression by the primary tumor.

Conclusions

The results of this study suggest that immunohistochemistry for P53 in the primary tumor could be useful in the clinical evaluation of patients with PTC. Moreover, P53 protein overexpression in lymph node metastasis may be useful as a treatment guide or target for lymph node recurrences.

Keywords

Thyroid Carcinoma Papillary Thyroid Carcinoma Metastatic Lymph Node Differentiate Thyroid Carcinoma Follicular Thyroid Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Kebebew E, Clark OH (2000) Differentiated thyroid cancer: “complete” rational approach. World J Surg 24(8):942–951PubMedCrossRefGoogle Scholar
  2. 2.
    Duntas L, Grab-Duntas BM (2006) Risk and prognostic factors for differentiated thyroid cancer. Hell J Nucl Med 9(3):156–162PubMedGoogle Scholar
  3. 3.
    Ito Y, Miyauchi A, Jikuzono T et al (2007) Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping. World J Surg 31(4):838–848PubMedCrossRefGoogle Scholar
  4. 4.
    Donghi R, Longoni A, Pilotti S et al (1993) Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland. J Clin Invest 91(4):1753–1760PubMedCrossRefGoogle Scholar
  5. 5.
    Fagin JA, Matsuo K, Karmakar A et al (1993) High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 91(1):179–184PubMedCrossRefGoogle Scholar
  6. 6.
    Nikiforov YE (2004) Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas. Endocr Pathol 15(4):319–327PubMedCrossRefGoogle Scholar
  7. 7.
    Hosal SA, Apel RL, Freeman JL et al (1997) Immunohistochemical localization of p53 in human thyroid neoplasms: correlation with biological behavior. Endocr Pathol 8(1):21–28PubMedCrossRefGoogle Scholar
  8. 8.
    Godballe C, Asschenfeldt P, Jorgensen KE et al (1998) Prognostic factors in papillary and follicular thyroid carcinomas: p53 expression is a significant indicator of prognosis. Laryngoscope 108(2):243–249PubMedCrossRefGoogle Scholar
  9. 9.
    Dobashi Y, Sakamoto A, Sugimura H et al (1993) Overexpression of p53 as a possible prognostic factor in human thyroid carcinoma. Am J Surg Pathol 17(4):375–381PubMedCrossRefGoogle Scholar
  10. 10.
    Karlidag T, Cobanoglu B, Keles E et al (2007) Expression of Bax, p53, and p27/kip in patients with papillary thyroid carcinoma with or without cervical nodal metastasis. Am J Otolaryngol 28(1):31–36PubMedCrossRefGoogle Scholar
  11. 11.
    Horie S, Maeta H, Endo K et al (2001) Overexpression of p53 protein and MDM2 in papillary carcinomas of the thyroid: correlations with clinicopathologic features. Pathol Int 51(1):11–15PubMedCrossRefGoogle Scholar
  12. 12.
    Zafon C, Obiols G, Castellvi J et al (2007) Clinical significance of RET/PTC and p53 protein expression in sporadic papillary thyroid carcinoma. Histopathology 50(2):225–231PubMedCrossRefGoogle Scholar
  13. 13.
    Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351(6326):453–456PubMedCrossRefGoogle Scholar
  14. 14.
    Ito T, Seyama T, Mizuno T et al (1992) Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland. Cancer Res 52(5):1369–1371PubMedGoogle Scholar
  15. 15.
    Freeman JL, Gershon A, Liavaag PG et al (1996) Papillary thyroid carcinoma metastasizing to the sphenoid-ethmoid sinuses and skull base. Thyroid 6(1):59–61PubMedGoogle Scholar
  16. 16.
    Lane DP, Benchimol S (1990) P53: oncogene or anti-oncogene? Genes Dev 4(1):1–8PubMedCrossRefGoogle Scholar
  17. 17.
    Fritsche M, Haessler C, Brandner G (1993) Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. Oncogene 8(2):307–318PubMedGoogle Scholar
  18. 18.
    Liu MC, Gelmann EP (2002) P53 gene mutations: case study of a clinical marker for solid tumors. Semin Oncol 29(3):246–257PubMedCrossRefGoogle Scholar
  19. 19.
    Park KY, Koh JM, Kim YI et al (1998) Prevalences of Gs alpha, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population. Clin Endocrinol (Oxf) 49(3):317–323CrossRefGoogle Scholar
  20. 20.
    Chen BK, Ohtsuki Y, Furihata M et al (1999) Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage. Int J Oncol 15(5):893–898PubMedGoogle Scholar
  21. 21.
    Zedenius J, Larsson C, Wallin G et al (1996) Alterations of p53 and expression of WAF1/p21 in human thyroid tumors. Thyroid 6(1):1–9PubMedCrossRefGoogle Scholar
  22. 22.
    Omar E, Madhavan M, Othman NH (2004) Immunohistochemical localisation of RET and p53 mutant protein of thyroid lesions in a north-eastern Malaysian population and its prognostic implications. Pathology 36(2):152–159PubMedCrossRefGoogle Scholar
  23. 23.
    Kataki A, Sotirianakos S, Memos N et al (2003) P53 and C-FOS overexpression in patients with thyroid cancer: an immunohistochemical study. Neoplasma 50(1):26–30PubMedGoogle Scholar
  24. 24.
    Ito Y, Jikuzono T, Higashiyama T et al (2006) Clinical significance of lymph node metastasis of thyroid papillary carcinoma located in one lobe. World J Surg 30(10):1821–1828PubMedCrossRefGoogle Scholar
  25. 25.
    Weisbart RH, Hansen JE, Chan G et al (2004) Antibody-mediated transduction of p53 selectively kills cancer cells. Int J Oncol 25(6):1867–1873PubMedGoogle Scholar
  26. 26.
    Hansen JE, Fischer LK, Chan G et al (2007) Antibody-mediated p53 protein therapy prevents liver metastasis in vivo. Cancer Res 67(4):1769–1774PubMedCrossRefGoogle Scholar
  27. 27.
    Rouxel A, Hejblum G, Bernier MO et al (2004) Prognostic factors associated with the survival of patients developing loco-regional recurrences of differentiated thyroid carcinomas. J Clin Endocrinol Metab 89(11):5362–5368PubMedCrossRefGoogle Scholar
  28. 28.
    Pineda JD, Lee T, Ain K et al (1995) Iodine-131 therapy for thyroid cancer patients with elevated thyroglobulin and negative diagnostic scan. J Clin Endocrinol Metab 80(5):1488–1492PubMedCrossRefGoogle Scholar
  29. 29.
    Mazzaferri EL, Kloos RT (2001) Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 86(4):1447–1463PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2008

Authors and Affiliations

  1. 1.Department of SurgeryTeikyo University School of MedicineTokyoJapan

Personalised recommendations