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Rationale for Testing TP53 Mutations in Thyroid Cancer-Original Data and Meta-Analysis.

Katarzyna Lacka1, Adam Maciejewski1, Piotr Tyburski2

  • 1Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland.

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Summary

TP53 mutations are common in anaplastic thyroid cancer (ATC) but rare in differentiated thyroid cancer (DTC). p53 overexpression is a marker in both DTC and ATC, warranting further study for prognostic value in DTC.

Keywords:
immunohistochemistrymeta-analysismutationp53thyroid cancer

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The p53 protein is a crucial tumor suppressor involved in tumorigenesis.
  • TP53 mutations are infrequent in differentiated thyroid cancer (DTC) but prevalent in anaplastic thyroid cancer (ATC).

Purpose of the Study:

  • To investigate the prognostic significance of TP53 mutations and surrogate markers (p53 expression, p53-Abs) in thyroid cancer.
  • To differentiate the role of TP53 alterations in DTC versus ATC.

Main Methods:

  • Original analysis of TP53 mutations via SSSP and direct sequencing in DTC, ATC, and control groups.
  • Immunohistochemical assessment of p53 expression in tissue samples.
  • Meta-analysis of 14 studies on TP53 mutations and p53 expression in thyroid cancer.

Main Results:

  • TP53 mutations were found in all ATC cases and 6.67% of DTC cases.
  • p53 overexpression was significantly higher in both DTC (26.67%) and ATC compared to controls.
  • Meta-analysis confirmed TP53 mutations are more frequent in ATC than controls (OR 8.95, p=0.02), but not significantly in DTC vs. controls (OR 1.87, p=0.33).
  • p53 overexpression (OR 7.99 for DTC, OR 64.37 for ATC) and serum p53-Abs positivity (OR 2.07 for PTC) were significantly elevated versus controls.

Conclusions:

  • TP53 mutations are key events in ATC development.
  • While p53 overexpression and serum p53-Abs are elevated in DTC, their prognostic value requires further investigation through prospective studies.