P53 and Rb tumor suppressor gene alterations in gastric cancer.
Inactivation of tumor suppressor genes has been frequently observed in gastric carcinogenesis. Our purpose was to study the involvement of p53, APC, DCC, and Rb genes in gastric carcinoma.


METHODS
Loss of heterozygosity of the p53, APC, DCC and Rb genes was studied in 22 gastric cancer tissues using polymerase chain reaction; single-strand conformation polymorphism of the p53 gene exons 5-6 and exons 7-8 was studied using 35S-dATP, and p53 expression was detected using a histological immunoperoxidase method with an anti-p53 clone.


CONCLUSIONS
No loss of heterozygosity was observed in any of these tumor suppressor genes; homozygous deletion was detected in the Rb gene in 23% (3/13) of the cases of intestinal-type gastric carcinoma. Eighteen (81.8%) cases showed band mobility shifts in exons 5-6 and/or 7-8 of the p53 gene. The presence of the p53 protein was positive in gastric cancer cells in 14 cases (63.6%). Normal gastric mucosa showed negative staining for p53; thus, the immunoreactivity was likely to represent mutant forms. The correlation of band mobility shift and the immunoreactivity to anti-p53 was not significant (P =.90). There was no correlation of gene alterations with the disease severity.


CONCLUSIONS
The inactivation of Rb and p53 genes is involved in gastric carcinogenesis in our environment. Loss of the Rb gene observed only in the intestinal-type gastric cancer should be further evaluated in association with Helicobacter pylori infection. The p53 gene was affected in both intestinal and diffuse histological types of gastric cancer.
Mattar
Rejane
R
Department of Gastroenterology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil. rejanemattar@hotmail.com
Nonogaki
Suely
S
Silva
Cleonice
C
Alves
Venancio
V
Gama-Rodrigues
Joaquim J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D017491:Genes, APC; D016163:Genes, DCC; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013274:Stomach Neoplasms / Q000235:genetics*