The prognostic significance of the aberrant extremes of p53 immunophenotypes in breast cancer

David P Boyle*, Darragh G McArt, Gareth Irwin, Charlotte S Wilhelm-Benartzi, Tong F Lioe, Elena Sebastian, Stephen McQuaid, Peter W. Hamilton, Jacqueline A James, Paul B Mullan, Mark A Catherwood, D Paul Harkin, Manuel Salto-Tellez

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Aims: The utility of p53 as a prognostic assay has been elusive. The aims of this study were to describe a novel, reproducible scoring system and assess the relationship between differential p53 immunohistochemistry (IHC) expression patterns, TP53 mutation status and patient outcomes in breast cancer.

Methods and Results: Tissue microarrays were used to study p53 IHC expression patterns: expression was defined as extreme positive (EP), extreme negative (EN), and non-extreme (NE; intermediate patterns). Overall survival (OS) was used to define patient outcome. A representative subgroup (n = 30) showing the various p53 immunophenotypes was analysed for TP53 hotspot mutation status (exons 4-9). Extreme expression of any type occurred in 176 of 288 (61%) cases. As compared with NE expression, EP expression was significantly associated (P = 0.039) with poorer OS. In addition, as compared with NE expression, EN expression was associated (P = 0.059) with poorer OS. Combining cases showing either EP or EN expression better predicted OS than either pattern alone (P = 0.028). This combination immunophenotype was significant in univariate but not multivariate analysis. In subgroup analysis, six substitution exon mutations were detected, all corresponding to extreme IHC phenotypes. Five missense mutations corresponded to EP staining, and the nonsense mutation corresponded to EN staining. No mutations were detected in the NE group.

Conclusions: Patients with extreme p53 IHC expression have a worse OS than those with NE expression. Accounting for EN as well as EP expression improves the prognostic impact. Extreme expression positively correlates with nodal stage and histological grade, and negatively with hormone receptor status. Extreme expression may relate to specific mutational status.

Original languageEnglish
Pages (from-to)340-352
Number of pages13
JournalHistopathology
Volume65
Issue number3
Early online date16 Apr 2014
DOIs
Publication statusPublished - Sep 2014

Keywords

  • Breast Neoplasms
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genes, p53
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Middle Aged
  • Mutation
  • Prognosis
  • Receptor, ErbB-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Reproducibility of Results
  • Retrospective Studies
  • Tissue Array Analysis
  • Tumor Suppressor Protein p53

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