Different Pattern of Allelic Loss in Epstein-Barr Virus-Positive Gastric Cancer With Emphasis on the p53 Tumor Suppressor Pathway

Am J Pathol. 2002 Oct;161(4):1207-13. doi: 10.1016/S0002-9440(10)64397-0.

Abstract

Both Helicobacter pylori (HP) and Epstein-Barr virus (EBV) have been implicated in carcinogenesis of the stomach. Fifty-seven gastric carcinomas were tested for microsatellite instability and allelic loss at several tumor suppressor loci using 21 polymorphic microsatellite markers. Furthermore, immunohistochemistry for p53 and DPC4/SMAD4 was performed. Results were analyzed according to HP and EBV status of the tumors, as assessed by immunohistochemistry and RNA in situ hybridization, respectively. Fractional allelic loss was lower in EBV-positive carcinomas (n = 15) when compared to EBV-negative carcinomas (P < 0.001). EBV positivity was inversely associated with allelic loss at specific markers on chromosomal arms 5q (APC), 17p (TP53), and 18q (DPC4/SMAD4). Allelic loss at the TP53 locus was not encountered in EBV-positive carcinomas, but occurred in 51% of EBV-negative carcinomas (P < 0.005). Moreover, none of the EBV-positive carcinomas showed unequivocal p53 immunopositivity in contrast to 39% of the EBV-negative carcinomas (P < 0.01). EBV-status was not related to microsatellite instability. There was no correlation between HP-status and any of the molecular alterations tested. In conclusion, EBV-positive gastric carcinomas follow a distinct pathogenesis at the molecular level, in which p53 is not, or differently inactivated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chromosome Mapping
  • Consensus Sequence
  • Dinucleotide Repeats / genetics
  • Female
  • Genes, p53*
  • Genetic Markers*
  • Helicobacter pylori / isolation & purification
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Loss of Heterozygosity*
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Neoplasm Staging
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / virology
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Genetic Markers
  • Tumor Suppressor Protein p53