Prognostic aspects of immunohistochemical assessment of cellular renewal and transcription factor SOX2 with precancerous changes in the gastric mucosa depending on the genotype of Helicobacter pylori in patients with various types of chronic gastritis

Abstract

The precancerous potential of chronic gastritis (CG) associated with H. pylori is discussed in numerous writings, and today, CG is central to precancerous conditions of the stomach. A convincing theoretical basis for such an assessment of chronic gastritis is its characteristic feature — an interruption of cell renewal with the proliferation phase predominating over the differentiation phase. However, the determination of the degree of proliferative activity and impaired differentiation of the epithelium of the gastric mucosa (GM) remains not fully understood. The goal of our study was the immunohistochemical evaluation of the expression of Ki-67, Cyclin D1, p53, CPP32, HER2 and the Sox2 transcription factor in GM epithelial cells in patients with H. pylori-associated chronic gastritis.. To accomplish this goal, histological, cytological, immunohistochemical, molecular genetic, morphometric and statistical research methods were used. We found that in chronic H. pylori-associated non-atrophic gastritis (CNG) compared with H. pylori (-), the GM epithelium renewal rate increased, characterized by a significant increase in the expression of caspase-3 and Ki-67 proliferation markers, cyclin D1 (p <0.001) with expansion of the proliferative compartment and apoptosis zones. Ki-67, Cyclin D1, and p53 expression in severe dysplasia (SD) of GM was significantly (p <0.05) higher than the mild in patients with chronic non-atrophic and atrophic H. pylori-associated gastritis, despite a decrease in the expression of the transcription factor Sox2 and caspase-3 in cases of SD. The most specific marker for determining SD in patients with H. pylori-associated chronic gastritis was marker p53 (sensitivity 98.73%; specificity 83.38%, confidence interval 95%, p <0.05). Considering the immunohistochemical markers of H. pylori, a screening system has been developed for the early diagnosis of precancerous changes in the GM that will help optimize the treatment tactics of patients with chronic gastritis and increase the efficiency of detecting dysplastic and atrophic changes in the GM at their early stages of development.