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Microsatellite instability in intestinal- and diffuse-type gastric carcinoma
G Buonsanti1, D Calistri, L Padovan
1Department of Genetics and Microbiology, University of Pavia, Italy.
The Journal of Pathology
|June 1, 1997
Summary
Genetic instability plays a key role in intestinal gastric cancer development, appearing early and increasing with progression. Its role in diffuse gastric cancer is less significant, with no clear association with p53 mutations.
Area of Science:
- Oncology
- Genetics
- Gastroenterology
Background:
- Gastric cancer comprises intestinal and diffuse histotypes.
- Genetic instability, specifically the replication error-positive (RER+) phenotype, is implicated in carcinogenesis.
- The role of genetic instability in different gastric cancer types and stages requires further elucidation.
Purpose of the Study:
- To investigate the role of genetic instability in the development of intestinal and diffuse-type gastric cancers.
- To compare the frequency of the RER+ phenotype in early and advanced stages of both histotypes.
- To explore the association between microsatellite instability and p53 gene mutations in gastric cancer.
Main Methods:
- Analysis of six microsatellite loci in 98 gastric carcinomas (intestinal and diffuse types) at early and advanced stages.
- Inclusion of five preneoplastic lesions in the analysis.
- Extended p53 gene mutation screening for all samples.
Main Results:
- RER+ phenotype frequency was significantly higher in intestinal (23%) than diffuse (5%) gastric cancers.
- RER+ frequency was slightly higher in advanced (19%) than early (12%) tumors overall.
- Instability at multiple loci and replication errors were observed in intestinal tumors and dysplasia, suggesting an early role.
Conclusions:
- Genetic instability plays an important and early role in intestinal-type gastric carcinogenesis.
- Genetic instability has a less significant role in diffuse-type gastric carcinogenesis.
- A trend towards a negative association between microsatellite instability and p53 mutations was observed in intestinal-type tumors.