MGMT Protein Expression in Chronic Gastritis as a Possible Marker for the Gastric Cancer Development Risk Assessment

Gastric cancer represents a heterogeneous group of tumors with distinct molecular mechanisms of development. One of the many molecular genetic alterations found in gastric cancer is inactivation of the O6-methylguanine-DNA methyltransferase (MGMT) gene.

The aim of the study was to evaluate MGMT protein expression in chronic gastritis as a potential predictive marker for gastric cancer risk.

Material and methods. The study material consisted of biopsy and surgical specimens of the gastric mucosa. The first group included 62 cases of sporadic gastric cancer, each represented by one tumor tissue fragment and one fragment from a distant zone of tumor growth. The second group comprised 58 gastric mucosal samples obtained during esophagogastroduodenoscopy from patients with dyspeptic complaints. Immunohistochemical staining was performed on paraffin sections of all specimens using mouse monoclonal antibodies against the MGMT protein (Diagnostic Bio Systems, USA; clone MT3.1, dilution 1:100) and the PolyVuePlus HRP/DAB detection system (Diagnostic Bio Systems, USA).

Results. In the gastric cancer samples, a marked decrease in the MGMT protein index was observed, down to 4 [2; 8] points. In the gastric mucosal fragments from the distant zone in the first group, a pronounced reduction in the MGMT protein index was also found, down to 4 [2; 6] points. In the second group of gastric mucosal biopsies, the MGMT protein index value remained at a high level — 9 [9; 12] points. Comparison of the distribution of MGMT protein index values demonstrated no differences between the gastric cancer samples and the distant-zone gastric mucosa (p = 0.56). At the same time, the decrease in the MGMT protein index in the distant-zone samples was statistically significantly different (p < 0.001) from the preserved level of MGMT protein expression in the biopsies of the second group.

Conclusion. The statistically significant decrease in the MGMT protein level in the distant zone of tumor growth compared with morphologically comparable gastric mucosa in chronic gastritis may serve as a potential predictor of gastric cancer risk.

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