title: Evidence that expression of a mutated p53 gene attenuates apoptotic cell death in human gastric intestinal-type carcinomas in vivo.
abstract: To examine in vivo the validity of the results of experiments in vitro, we analyzed the relationship between p53 gene status and apoptotic cell death of human gastric intestinal-type adenocarcinomas. Surgical specimens were classified into two categories: 18 gastric cancers with nuclear p53 protein (A), and 17 gastric cancers without nuclear p53 protein (B). Polymerase chain reaction-single strand conformation polymorphism disclosed a shifted band that corresponded to a mutation in the p53 gene in 13 cases (72%) in category A and 3 cases (18%) in category B, the frequency being significantly higher in the former (P < 0.05). Apoptotic cells were identified from routinely stained sections and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The TUNEL index [TI; (the number of TUNEL-positive apoptotic cells/the total number of tumor cells) x 100] was 3.8 +/- 1.4% in category A and 4.9 +/- 1.2% in category B, the value being significantly lower in the former (P < 0.05). The proliferating cell nuclear antigen index, defined similarly to the TI, was 56.4 +/- 16.3% in category A, and it was significantly higher than that in category B (P < 0.05). The immunohistochemically detected expression of p21CIP1/WAP1 did not differ between the two categories, while Bax-positive tumor cells were more frequently detected in category A. These results indicate that (1) expression of a mutated p53 gene attenuates apoptotic cell death of gastric cancer, in accordance with the previous in vitro finding that p53 gene mutation provides a possible selective advantage for tumor cell proliferation, and (2) apoptosis is related not only to expression of p53 and the stage of the cell cycle, but also to p53-independent and cell cycle-independent events.
authors.affiliation: First Department of Pathology, Faculty of Medicine, Tottori University, Yonago.
authors.forename: M
authors.initials: M
authors.lastname: Ishida
authors.forename: Y
authors.initials: Y
authors.lastname: Gomyo
authors.forename: S
authors.initials: S
authors.lastname: Ohfuji
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
authors.forename: H
authors.initials: H
authors.lastname: Ito
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D017209:Apoptosis / Q000235:genetics*; D002467:Cell Nucleus / Q000737:chemistry; D004249:DNA Damage; D016158:Genes, p53; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53