Epstein-Barr virus-associated gastric lymphomas are distinct from mucosa-associated lymphoid tissue-type lymphomas: Genetic abnormalities of p53 gene

The authors studied 46 primary gastric lymphomas for expression of the p53 gene by immunohistochemistry and screened for mutations in p53 exon 5-8 by polymerase chain reaction-single strand conformation polymorphism. Twenty-f ive specimens cases were also analyzed for loss of heterozygosity (LOH) of chromosomal region 17p12-13.1. In 36 lymphomas negative for Epstein-Barr vi rus (EBV) infection, of which 29 were of mucosa-associated lymphoid tissue (MALT) type, p53 genetic changes were found in 47.2% but correlated poorly with overexpression. Only 20% of the mutations involved exon 7. There were recurrent mutations of intron 7, intron 6, and exon 6. In contrast, the 10 EBV-positive cases, none of MALT type, had a much higher rate of mutation, and all showed both p53 overexpression and p53 mutation and/or LOH, and 87. 5% had mutations involving exon 7. Four of these involved codon 242, not se en in the EBV-negative group. Splicing mutations of intron 8 were seen in t hree specimens, two involving the same nucleotide position. In four of five specimens, LOH analysis identified microsatellite instability, allelic los s, or both. The Helicobacter pylori infection rate in the EBV-positive grou p (20%) was much lower than in the EBV-negative group (91.7%). These differ ences between the two groups suggest involvement of different carcinogens. Mutation of codon 242 has not been specifically associated with other tumor s and may represent a mutational hot spot in the EBV-positive lymphomas.