Gastric Precancerous Lesions: From Progenitor Cell and Microsatellite Instability to Clinical Interpretation of Gastric Cancer Risk

Aim: to evaluate the possibility of the MMR-system status, microsatellite instability (MSI) usage in the differential diagnosis of gastric mucosa dysplasia, determination of the gastric adenocarcinoma development risk. Material and methods. The study included gastric mucosa specimens of 75 patients: 25 with high-grade dysplasia, 25 with low-grade dysplasia, 25 were indefinite for dysplasia. Gastrobiopsy specimens were examined histologically, immunohistochemically using mouse monoclonal antibodies (Diagnostic BioSystems, USA) to the MMR system proteins: MLH-1 (clone G168-15, dilution 1:50), MSH2 (clone DBM15.82, dilution 1:100), MSH6 (clone 44, dilution 1:50), PMS2 (clone A16-4, ready to use). 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. VOSviewer (1.6.20) was used to visualize the bibliometric analysis. Results. MMR-deficient cases were found in low (2.8 %) and high-grade (2.8 %) dysplasia with the immunohistochemical evaluation of MMR-system proteins in gastric mucosa specimens. In all indefinite for dysplasia cases MMR-system proteins remained unaffected. Three MSI-positive cases (6.5 %) were detected by PCR with two low-grade dysplasia, one high-grade dysplasia cases. All identified cases were also immunohistochemically MSI-positive. Conclusion. Determination of MSI can be used as an auxiliary study within a panel of biomarkers aimed to support the decision-making of a pathologist in the alternative of “indefinite for dysplasia” or “definite dysplasia — obligate precancer”.