Loss of p53 in esophageal squamous cell carcinoma and the correlation with survival: analyses of gene mutations, protein expression, and loss of heterozygosity in Japanese patients

J Surg Oncol. 2011 Aug 1;104(2):169-75. doi: 10.1002/jso.21920. Epub 2011 Apr 1.

Abstract

Background: A high frequency of p53 protein expression or gene mutation has been reported in the early stages of esophageal squamous cell carcinoma (ESCC), and thus loss of p53 function is thought to be very important in esophageal carcinogenesis. However, there is controversy surrounding the correlation between p53 dysfunction and ESCC tumor progression. The complexity arises from the different modalities, such as mutation analysis, immunohistochemistry, and the detection of loss of heterozygosity (LOH) at the p53 genomic locus.

Methods: In this study, we comprehensively analyzed p53 gene mutation, p53 protein expression, and LOH at 17p13 in 94 surgically resected Japanese cases of ESCC.

Results: The frequency of p53 gene mutation was 60.6%. The rate of positive p53 protein expression was 56.4%. The frequency of LOH at 17p13 was 67.5%. There was a statistically significant correlation between the presence of a gene mutation and LOH, whereas, there was no significant correlation between gene mutation and protein expression.

Conclusions: Despite the importance of loss of p53 function in esophageal carcinogenesis, none of the examined parameters, either singly or combined, correlated with overall survival. Taken together, p53 function is a primary target for esophageal carcinogenesis but there is no apparent correlation with the malignant phenotype in ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian Continental Ancestry Group / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / surgery
  • DNA Mutational Analysis
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / surgery
  • Female
  • Genes, p53 / genetics*
  • Humans
  • Immunohistochemistry
  • Loss of Heterozygosity*
  • Male
  • Middle Aged
  • Mutation
  • Survival Analysis
  • Tumor Suppressor Protein p53 / biosynthesis*

Substances

  • Tumor Suppressor Protein p53