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p53 gene mutations in gastric adenomas
H Tohdo1, H Yokozaki, K Haruma
1Department of Pathology, Hiroshima University School of Medicine, Japan.
Abstract:
p53 gene alterations in ten gastric adenomas and one carcinoma arising in an adenoma were analyzed by deoxynucleotide sequencing. Three (30%) of the ten gastric adenomas had p53 gene mutations, one adenoma showing a frameshift mutation and two others showing silent mutations. In addition, two missense mutations occurred in the carcinoma arising in an adenoma. Histologically, the adenomas containing silent mutations revealed moderate dysplasia. Immunoreactivity to p53 protein was also examined in 61 gastric adenomas, 19 carcinomas arising in adenomas and 48 early well-differentiated adenocarcinomas of the stomach (these included the tumors analyzed by deoxynucleotide sequencing). No staining for p53 was seen in the pure adenomas, but positive immunoreactivity was observed in 27% of the adenocarcinomas and 10.5% of the carcinomas arising in adenomas. These results suggest that p53 gene mutation is an early event in gastric carcinogenesis and missense mutation may play a crucial role in the conversion from adenoma to adenocarcinoma.
Insights
p53 gene mutations are early events in gastric cancer development. Missense mutations in the p53 gene may drive the progression from gastric adenoma to adenocarcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Gastric adenomas are precancerous lesions.
- The p53 tumor suppressor gene plays a critical role in cancer development.
Purpose of the Study:
- To investigate p53 gene alterations in gastric adenomas and associated carcinomas.
- To determine the role of p53 mutations in gastric carcinogenesis.
Main Methods:
- Deoxynucleotide sequencing was used to analyze p53 gene mutations in gastric adenomas and carcinomas.
- Immunohistochemistry was employed to detect p53 protein expression in gastric lesions.
Main Results:
- 30% of gastric adenomas exhibited p53 gene mutations, including frameshift and silent mutations.
- The carcinoma arising in an adenoma showed two missense mutations.
- p53 protein was not detected in pure adenomas but was present in 27% of adenocarcinomas and 10.5% of carcinomas arising in adenomas.
Conclusions:
- p53 gene mutation appears to be an early event in gastric carcinogenesis.
- Missense mutations in the p53 gene may be critical for the transition from adenoma to adenocarcinoma.