The relation of p53 gene mutations to gastric cancer subsite and phenotype

Objectives: We investigated p53 gene mutations in advanced gastric cancers by direct DNA sequencing, in order to determine the frequency of mutations in gastric cancers having different epidemiological backgrounds, tumors of the cardia were compared with those arising in the antrum or corpus. Intestinal type cancers were compared with diffuse or other histologic types. We have chosen to assess the frequency of mutations solely based on DNA sequencing. Methods: Paraffin embedded tissues from 100 gastric cancers were evaluated. The mutational status of the p53 gene in exons 5 through 9 were determined by direct sequencing of PCR products. Results: Mutations in exons 5, 6, 7 and 8 were found in 35 of 100 (35%) stomach cancers. One tumor had mutations in both exons 5 and 8. No mutations were detected in exon 9. p53 gene mutations were significantly more frequent in cancers of the cardia (19/35; 54%) than the antrum and corpus (16/65 (25%)) (p less than or equal to 0.005). p53 mutations were more frequent in intestinal type cancers (28/67; 42%) than diffuse cancers or other histologic types of cancer (7/33; 21%), but the difference was not statistically significant. Conclusions: Cancers of the cardia more frequently contain p53 mutations than do antral and corpus cancers, suggesting that cancers in the proximal and distal stomach evolve through different molecular pathways.