Association of p53 gene and protein alterations with metastases in colorectal cancer

Am J Surg Pathol. 1995 Apr;19(4):463-71. doi: 10.1097/00000478-199504000-00008.

Abstract

Using monoclonal antibody PAb 1801, p53 protein was detected in the neoplastic cells of 39 (46.9%) of 83 colorectal carcinomas studied. Patients with p53+ tumors showed a higher incidence of lymph node and liver metastases (p = 0.035); in patients whose tumors were located in the rectosigmoid, p53 expression also correlated with a more advanced stage according to Dukes' classification (p = 0.015) as well as nodal (p = 0.006) and liver (p = 0.019) metastases. Following amplification of exons 5 to 8 of the p53 gene by means of the polymerase chain reaction technique, single-strand conformation polymorphism analysis disclosed an anomalous migration pattern in 23 of the 39 p53+ tumors and in four of the 35 p53- tumors analyzed. Sequence analysis showed G:C-->A:T transitions in 63.6%, G:C-->T:A and G:C-->C:G transversions in 18.2%, deletions and insertions in 13.6%, and A:T-->G:C transitions in 4.6% of the cases. Loss of heterozygosity was studied in the DNA of 79 patients; allelic loss was found in 29 (49.1%) of the 59 informative patients. Loss of heterozygosity was correlated with p53 overexpression (p = 0.0002) as well as with the presence of mutations as detected by single strand conformation polymorphism analysis (p = 0.0024).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / secondary*
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / secondary*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, p53 / genetics*
  • Heterozygote
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Sequence Analysis, DNA
  • Tumor Suppressor Protein p53 / biosynthesis*

Substances

  • Tumor Suppressor Protein p53