TP53 mutation analyses on breast carcinomas: a study of paraffin-embedded archival material

Br J Cancer. 1996 Aug;74(4):555-61. doi: 10.1038/bjc.1996.400.

Abstract

The aim of this investigation was to examine the possibility of analysing TP53 mutations in archival paraffin-embedded material with the constant denaturant gel electrophoresis (CDGE) method. We extracted DNA from 193 archival primary breast carcinoma samples, diagnosed in 1981-83; further analysis was possible for 186 of these. TP53 mutations in exons 5-8 were detected with CDGE in 30 samples (16.1%) and 17 of these mutations were confirmed by sequencing. Immunohistochemistry demonstrated TP53 nuclear accumulation in 58 tumours (31%). A strong association between the presence of TP53 mutations and TP53 immunostaining was observed (P < 0.001). Our mutation and immunohistochemistry results are in agreement with other findings based on fresh tumour tissue. TP53 abnormalities were significantly related to high S-phase fraction, low oestrogen receptor (ER) content and high tumour grade. Survival of patients with TP53 abnormalities, in the group as a whole, did not differ from patients with normal TP53. Our study did, however, show that patients with abnormal TP53 had a significantly shorter post-recurrence survival (P = 0.005) than patients with normal TP53.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / pathology
  • Conserved Sequence
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / isolation & purification*
  • Disease-Free Survival
  • Exons
  • Female
  • Frameshift Mutation
  • Genes, p53*
  • Histological Techniques
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Middle Aged
  • Mutation*
  • Neoplasm Invasiveness
  • Paraffin
  • Ploidies
  • Point Mutation
  • Polymerase Chain Reaction
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Recurrence
  • S Phase
  • Sequence Deletion
  • Survival Rate
  • Tumor Suppressor Protein p53 / analysis*

Substances

  • DNA, Neoplasm
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tumor Suppressor Protein p53
  • Paraffin