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Related Experiment Videos

Correlation between p53 immunostaining patterns and gene sequence mutations in breast carcinoma

D W Visscher1, F H Sarkar, R K Shimoyama

  • 1Department of Pathology, Harper Hospital, Detroit, MI 48201, USA.

Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B
|September 1, 1996
PubMed
Summary

Assessing p53 protein in breast cancer using two antibodies revealed discrepancies. Staining patterns did not always correlate with gene mutations, and both antibodies indicated a poorer prognosis for patients with invasive breast carcinomas.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pathology

Background:

  • The tumor suppressor protein p53 plays a crucial role in preventing cancer.
  • Immunohistochemistry is commonly used to assess p53 protein levels in tumors.
  • Discrepancies in p53 immunostaining can arise due to various factors, impacting diagnostic accuracy.

Purpose of the Study:

  • To evaluate the concordance between two commercial p53 antibodies (DO7 and PAb1801) in invasive breast carcinomas.
  • To investigate the correlation between p53 immunostaining patterns and p53 gene mutations.
  • To determine the prognostic significance of p53 immunostaining in breast cancer patients.

Main Methods:

  • p53 immunostaining was performed on 82 invasive breast carcinomas using DO7 (formalin-fixed) and PAb1801 (acetone-fixed) antibodies.

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  • Single-strand conformational polymorphism (SSCP) analysis and DNA sequencing of exons 2-11 were conducted on 18 selected cases.
  • Disease recurrence data was collected for prognostic analysis.

    • Main Results:

    • DO7 stained more cases (52%) than PAb1801 (33%), but DO7 staining was often heterogeneous or focal.
    • p53 gene mutations were found in 33% of cases negative for DO7 staining, with some showing PAb1801 reactivity.
    • Tumors with mutations often exhibited heterogeneous or focal DO7 staining, while those lacking mutations showed immunoreactivity with both antibodies.
    • Both antibodies were significantly associated with adverse patient outcomes (disease recurrence).

    Conclusions:

    • Discrepancies in p53 immunostaining can result from fixation artifacts, antibody specificities, and "silent" mutations.
    • Aberrant overexpression of wild-type p53 protein may also contribute to varied staining results.
    • p53 immunostaining, despite potential discrepancies, is a significant prognostic marker in invasive breast carcinoma.