In situ quantification of aberrant p53 in colorectal neoplasia

Steven Jay Smith, Alfred Neugut, Daniel Heitjan, Kenneth Forde, Peter Holt, Regina M. Santella, Luo Jiin-Chyuan, Walter Carney, Llewelyn Ward, Paul W. Brandt-Rauf

Research output: Contribution to journalArticle

Abstract

Aberrant p53 protein accumulation was measured immunohistologically in 342 colorectal paraffin-embedded tissue sections from 115 patients (24 with adenocarcinoma, 59 with adenoma and 32 'hospital controls'). Subjective scoring was compared with quantitative cell imaging, including dichotomous (p53+/p53-) status, ng p53mut mg-1 enterocyte protein, and tumour burden and patient body 'burden' of aberrant p53. A total of 62.5% cancer patients, 23.7% adenoma patients and 3.1% hospital controls were accorded p53+ status on the basis of p53 quantification. Quantitative p53+/p53- assignment had a stronger inverse association with survival (χ2 = 6.17, p = 0.013, Kaplan-Meier test) than subjective 'visual estimation' (χ2 = 0.57, p = 0.449). There was a strong inverse relationship between the p53 'body burden' and the months of post-diagnosis survival (hazard ratio = 1.42, p = 0.0004, Cox proportional hazards). Absolute quantification for inactivated p53 permits objective and reproducible scoring, adjusts for intra-laboratory immunostaining 'batch effects', corrects for fixation artefacts, and standardizes for inter-laboratory differences in fixation, antibody selection and staining method. Clinically, in situ quantification of p53 will permit more accurate survival prognoses and will inform therapy selection and dose. Ultimately, accurate quantitative tissue/blood p53 correlations may provide a minimally invasive and systemic surrogate measure for these same clinical purposes.

Original languageEnglish (US)
Pages (from-to)311-332
Number of pages22
JournalBiomarkers
Volume8
Issue number4/3
DOIs
StatePublished - May 1 2003

Keywords

  • Cell imaging densitometry
  • Colorectal
  • Immunohistochemistry
  • Protein quantitation
  • Tumour/tumour tissue
  • p53

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Health, Toxicology and Mutagenesis

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