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[Microsatellite instability as a possible diagnostic marker of the gastric mucosa dysplasia]
A V Kononov1, V A Rubtsov1, M N Parygina1
1Omsk State Medical University, Omsk, Russia.
Objective:
To evaluate the MMR system proteins and the MSI status of regenerative (indefinite for dysplasia) and pronounced (epithelial dysplasia) gastric mucosa precancerous lesions in the comparison with cancer to determine their possible potential as a diagnostic markers of gastric mucosa dysplasia.
Material And Methods:
The study included 2 groups of gastric mucosa specimens: (1) 150 biopsy gastric mucosa specimens: 43 with low-grade dysplasia, 32 with high-grade dysplasia, 75 - indefinite for dysplasia; (2) 155 cancer tissue specimens from resected stomachs. Gastric mucosa specimens were examined histologically, immunohistochemically using mouse monoclonal antibodies to the MMR system proteins: MLH-1, MSH2, MSH6, PMS2 (Diagnostic BioSystems, USA). MSI was studied with multiplex PCR evaluation of DNA microsatellites (NR-21, NR-24, NR-27, BAT-25, BAT-26) from paraffin sections, their analysis with capillary electrophoresis. The obtained data were processed with the Statistica 10.0 (StatSoft, USA), presented using descriptive, analytical statistics.
Results:
MSI was detected by immunohistochemistry in 8% (n=6) of the studied cases of low/high grade dysplasia, which does not have statistically significant differences from the distribution of MSI in the gastric cancer group (12% of microsatellite-unstable cases (n=18)) (p=0.49). MSI was not detected in any indefinite for dysplasia case.
Conclusion:
Detection of microsatellite instability in gastric mucosa dysplasia indicates the likelihood of its occurrence at the early stages of the carcinogenesis cascade and makes it possible to use it to assess the risk of gastric cancer associated with microsatellite instability. The absence of instability in cases indefinite for dysplasia determines the possibility of its use for differential diagnosis of truly neoplastic and regenerative/reactive changes in the gastric mucosa.
Insights
Microsatellite instability (MSI) is present in gastric precancerous lesions, suggesting its role in early gastric cancer development. Absence of MSI in indefinite dysplasia cases aids differential diagnosis of neoplastic changes.
Area of Science:
- Gastroenterology
- Oncology
- Molecular Diagnostics
Context:
- Gastric precancerous lesions, including indefinite for dysplasia and epithelial dysplasia, represent a critical stage in gastric carcinogenesis.
- Understanding the molecular alterations in these lesions is crucial for early detection and prevention of gastric cancer.
Purpose:
- To evaluate the expression of mismatch repair (MMR) system proteins and the status of microsatellite instability (MSI) in precancerous gastric mucosa.
- To compare these markers in regenerative (indefinite for dysplasia) and pronounced (epithelial dysplasia) lesions with gastric cancer.
- To determine their potential as diagnostic markers for gastric mucosa dysplasia.
Summary:
- The study analyzed 150 gastric mucosa biopsy specimens and 155 gastric cancer tissues using immunohistochemistry for MMR proteins (MLH-1, MSH2, MSH6, PMS2) and multiplex PCR for MSI analysis.
- MSI was detected in 8% of low/high-grade dysplasia cases and 12% of gastric cancer cases, with no statistically significant difference (p=0.49).
- Crucially, MSI was not detected in any cases classified as indefinite for dysplasia.
Impact:
- Detection of MSI in gastric dysplasia suggests its involvement in early gastric carcinogenesis, potentially serving as a risk assessment marker for gastric cancer.
- The absence of MSI in indefinite dysplasia cases supports its utility in differentiating truly neoplastic changes from regenerative or reactive alterations in the gastric mucosa.
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