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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations.

You-Na Sung1, Deokhoon Kim1, Jihun Kim2

  • 1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea.

Diagnostic Pathology
|December 5, 2022
PubMed
Summary

p53 immunohistochemical staining (IHC) patterns effectively predict TP53 gene mutations in solid cancers. MDM2 amplification status does not influence p53 IHC patterns, aiding cancer diagnosis and treatment.

Keywords:
AssociationImmunohistochemistryMutationTP53 genep53 protein

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • TP53 is the most frequently mutated gene in human cancers.
  • Understanding TP53 mutational status is crucial for cancer patient diagnosis and treatment.
  • MDM2 acts as a negative regulator of p53.

Purpose of the Study:

  • To investigate the association between TP53 gene mutations and p53 immunohistochemical staining (IHC) patterns.
  • To evaluate the non-genetic effect of MDM2 on p53 IHC patterns.

Main Methods:

  • 135 solid cancer cases with next-generation sequencing data were analyzed.
  • p53 IHC was performed and patterns (overexpression, null type, usual) were classified.
  • TP53 mutations were annotated into DISRUPTED and IF-DBD categories.

Main Results:

  • TP53 mutations were observed in 77.0% of cases.
  • Null type p53 IHC pattern correlated with DISRUPTED TP53 mutations (86.2% sensitivity, 97.2% specificity).
  • Overexpression p53 IHC pattern correlated with IF-DBD TP53 mutations (100% sensitivity, 81.7% specificity).
  • Usual p53 IHC pattern showed 100% specificity for predicting wild-type TP53.
  • p53 IHC patterns showed a perfect association with TP53 mutation patterns, irrespective of MDM2 amplification.

Conclusions:

  • p53 IHC patterns (overexpression, null type, usual) are reliable predictors of TP53 mutational status (DISRUPTED, IF-DBD).
  • MDM2 amplification status does not impact p53 IHC patterns.