Skip to main content
SpringerLink
Log in

Immunohistochemical localization of p53 in human thyroid neoplasms: Correlation with biological behavior

  • Clinical Research
  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only 5 of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extrathyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.

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. Murray D. The thyroid gland. In: Kovacs K, Asa SL, eds. Functional endocrine pathology. Boston, MA: Blackwell Scientific, 1991; 293–374.

    Google Scholar 

  2. LiVolsi VA. Surgical pathology of the thyroid. Philadelphia, PA. Saunders, 1990.

    Google Scholar 

  3. Rosai J, Carcangiu ML, DeLellis RA. Tumors of the thyroid gland. Atlas of tumor pathology, 3rd ser, Fascicle 5, Washington, DC: Armed Forces Institute of Pathology, 1992.

    Google Scholar 

  4. Weinberg RA. Tumor suppressor genes. Science 254:1138–1146, 1991.

    Article  PubMed  CAS  Google Scholar 

  5. Levine AJ. The p53 tumor-suppressor gene. N Engl J Med 326:1350–1352, 1992.

    Article  PubMed  CAS  Google Scholar 

  6. Wynford-Thomas D. p53 in tumour pathology: can we trust immunocytochemistry? J Pathol 166:329,330, 1992.

    Article  PubMed  CAS  Google Scholar 

  7. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins RS, Weston A, Modali R, Harris CC, Vogelstein B. Mutations in the p53 gene occur in diverse human tumour types. Nature 342:705–708, 1989.

    Article  PubMed  CAS  Google Scholar 

  8. Porter PL, Gown AM, Kramp SG, Coltrera MD. Widespread p53 overexpression in human malignant tumors. Am J Pathol 140:145–153, 1992.

    PubMed  CAS  Google Scholar 

  9. Barbareschi M, Iuzzolino P, Pennella A, Allegranza A, Arrigoni G, Dalla Palma P, Doglioni C. p53 protein expression in central nervous system neoplasms. J Clin Pathol 45:583–586, 1992.

    Article  PubMed  CAS  Google Scholar 

  10. Shea CR, McNutt NScott, Volkenadt M, Lugo J, Prioleau PG, Albinot AP. Over-expression of p53 protein in basal cell carcinomas of human skin. Am J Pathol 141: 25–29, 1992.

    PubMed  CAS  Google Scholar 

  11. Fagin JA. Genetic basis of endocrine disease 3. Molecular defects in thyroid gland neoplasia. J Clin Endocrinol Metab 75:1398–1400, 1992.

    Article  PubMed  CAS  Google Scholar 

  12. Farid NR, Shi Y, Zou M. Molecular basis of thyroid cancer. Endocr Rev 15:202–232, 1994.

    Article  PubMed  CAS  Google Scholar 

  13. Fagin JA, Matsuo K, Karmakar A, Chen DL, Tang S-H, Koeffler HP. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 91:179–184, 1992.

    Google Scholar 

  14. Donghi R, Longoni A, Pilotti S, Michieli P, Della Porta G, Piarotti MA. Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland. J Clin Invest 91:1753–1760, 1993.

    PubMed  CAS  Google Scholar 

  15. Nakamura T, Yana I, Kobayashi T, Shin E, Karakawa K, Fujita S, Miya A, Mori T, Nishisho I, Takai S. p53 gene mutations associated with anaplastic transformation of human thyroid carcinomas. Jpn J Cancer Res 83:1293–1298, 1992.

    PubMed  CAS  Google Scholar 

  16. Ito T, Seyama T, Mizuno T, Tsuyama N, Hayashi T, Hayashi Y, Dohi K, Nakamura N, Aklyama M. Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland. Cancer Res 52:1369–1371, 1992.

    PubMed  CAS  Google Scholar 

  17. Wyllie FS, Lemoine NR, Williams ED, Wynford-Thomas D. Structure and expression of nuclear oncogenes in multi-stage thyroid tumorigenesis. Br J Cancer 60:561–565, 1989.

    PubMed  CAS  Google Scholar 

  18. Zou M, Shi Y, Farid NR. p53 mutations in all stages of thyroid carcinomas. J Clin Endocrinol Metab 77:1054–1058, 1993.

    Article  PubMed  CAS  Google Scholar 

  19. Dobashi Y, Sakamoto A, Sugimura H, Mernyei M, Mori M, Oyama T, Machinami R. Overexpression of p53 as a possible prognostic factor in human thyroid carcinoma. Am J Surg Pathol 17:375–381, 1993.

    Article  PubMed  CAS  Google Scholar 

  20. Soares J, Cameselle-Teijeiro J, Sobrinho-Simoes M. Immunohistochemical detection of p53 in differentiated, poorly differentiated and undifferentiated carcinomas of the thyroid. Histopathology 24:205–210, 1994.

    Article  PubMed  CAS  Google Scholar 

  21. Pilotti S, Collini P, Del Bo R, Cattoretti G, Pierotti MA, Rilke F. A novel panel of antibodies/hat segregates immunocytochemically poorly differentiated carcinoma from undifferentiated carcinoma of the thyroid gland. Am J Surg Pathol 18:1054–1064, 1994.

    Article  PubMed  CAS  Google Scholar 

  22. Shi S-R, Key ME, Kalra KL. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39:741–748, 1991.

    PubMed  CAS  Google Scholar 

  23. Ogden GR, Kiddie RA, Lunny DP, Lane DP. Assessment of p53 protein expression in normal, benign, and malignant oral mucosa. J Pathol 166:389–394, 1992.

    Article  PubMed  CAS  Google Scholar 

  24. van der Lean BFAM, Freeman JL, Tsang RW, Asa SL. The association of well-differentiated thyroid carcinoma with insular or anaplastic thyroid carcinoma: evidence for dedifferentiation in tumor progression. Endocr Pathol 4:215–221, 1993.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Otolaryngology Mount Sinai Hospital, University of Toronto, 600 University Avenue, M5G 1X5, Toronto, Canada

    Sefik A. Hosal MD & Jeremy L. Freeman MD

  2. Department of Pathology Mount Sinai Hospital, University of Toronto, 600 University Avenue, M5G 1X5, Toronto, Canada

    Robyn L. Apel BS, MB & Sylvia L. Asa MD, PhD

  3. Department of Surgery Mount Sinai Hospital, University of Toronto, 600 University Avenue, M5G 1X5, Toronto, Canada

    Abbas Azadian MD & Irving B. Rosen MD

  4. Department of Pathology, University of Pennsylvania Medical Center, Philadelphia, PA

    Virginia A. LiVolsi MD

Authors
  1. Sefik A. Hosal MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robyn L. Apel BS, MB
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeremy L. Freeman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abbas Azadian MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Irving B. Rosen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Virginia A. LiVolsi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sylvia L. Asa MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hosal, S.A., Apel, R.L., Freeman, J.L. et al. Immunohistochemical localization of p53 in human thyroid neoplasms: Correlation with biological behavior. Endocr Pathol 8, 21–28 (1997). https://doi.org/10.1007/BF02739704

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02739704

Key Words

Search

Navigation