Comparative analysis of p53 gene mutations and protein accumulation in human non-small-cell lung cancer

Int J Cancer. 1995 Apr 21;64(2):83-91. doi: 10.1002/ijc.2910640203.


A series of 54 resected primary non-small-cell lung carcinomas was analyzed for p53 gene mutations and for p53 protein accumulation and the findings were correlated with clinical parameters. Mutations in exons 5 through 8 of the p53 gene were identified by a denaturing gradient gel electrophoresis (DGGE) assay and cycle sequencing, whereas p53 protein accumulation was detected in paraffin-embedded tissue by immunostaining using 2 different murine monoclonal antibodies (MAbs) (BP53-12 and DO7). A p53 gene mutation and/or p53 protein accumulation was found in 37 of 54 tumors. Mis-sense mutations were closely associated with positive immunostaining, which was intense in 15 out of 17 cases with a mutation. In 10 tumors, obvious p53 accumulation was detected in the absence of mutations in exons 5 through 8. Conversely, only one of 8 p53 non-sense mutations led to detectable p53 accumulation. The most frequent single base changes were G --> T transversions and C --> T transitions. The presence of a p53 alteration was not related to age, tumor size, stage or histology. However, we found a significant inverse correlation between p53 alterations and the presence of a K-ras mutation. This was reflected in the overall postoperative survival data: patients with p53 alterations in their tumors tended to have a better prognosis than those without a p53 alteration; however, this difference was lost when cases with a K-ras mutation were omitted from the analysis.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / chemistry*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Electrophoresis, Polyacrylamide Gel
  • Exons
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, p53 / genetics*
  • Genes, ras
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / chemistry*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Survival Analysis
  • Tumor Suppressor Protein p53 / analysis*
  • Tumor Suppressor Protein p53 / genetics


  • Tumor Suppressor Protein p53