In the dissertation it was revealed that gastric hyperplastic polyps are characterized by the average proliferation level and the low apoptosis level of epitheliocytes, the low proliferation level and the average apoptosis level of stromal cells, the tendency to express gastric mucins and also by the low levels of cells stromolytic activity. The leading role in gastric hyperplastic polyps progression is played by epithelial dysplasia with the increasing levels of proliferation, p53 oncoprotein accumulation and Cdx-2 expression and also by the increased expression of MMP-2 by epithelium and stromal cells, that is countervailed by the increased expression of TIMP-1 by stromal cells. Progression of gastric hyperplastic polyps may lead to the development of intestinal-type gastric adenocarcinoma.
Intestinal-type gastric adenocarcinoma is characterized by the average levels of proliferation and apoptosis of cancer cells, the low levels of proliferation and apoptosis of stromal cells, the average levels of gastric-type and intestinal-type mucins expression and also by the low MMP-2 and TIMP-1 expression levels by cancer cells and the average expression levels of these markers by stromal cells. In comparison with gastric hyperplastic polyps it’s characterized by the higher levels of cell proliferation, p53 accumulation, apoptosis, expression of intestinal phenotype markers and stromolytic activity of cancer cells against the background of the reduced levels of stromal cells apoptosis and gastric-type mucins expression.
Non-invasive intestinal-type gastric adenocarcinoma, in comparison with non-changed gastric mucosa, is characterized by the higher levels of cell proliferation, p53 accumulation and apoptosis of cancer cells, against the background of the reduced level of gastric-type mucins expression by cancer cells, expression of intestinal-type mucins by cancer cells and expression of stromolytic activity markers by stromal cells. Moreover, it’s characterized by the decreased transcriptional activity of KRAS gene, that correlates with the increased EGFR and HER-2/neu expression levels, the decreased transcriptional activity of CDH1 gene, that correlates with the low
E-cadherin expression level, the increased transcriptional activity of CTNNB1 gene mRNA, that correlates with the high β-catenin expression level. The latter determines an active role of Wnt/β-catenin signaling pathway in reducing intercellular adhesion at early stage of the carcinoma development.
Invasive intestinal-type gastric adenocarcinoma differs from non-invasive one by the higher levels of apoptosis markers expression, the lower frequency of MUC5AC expression and the higher median of Cdx-2 expression, the higher frequency of
MMP-2 and the lower level of TIMP-1 expression by cancer cells, and also by the higher frequency and level of MMP-2 expression by stromal cells. The latter indicates a leading role of stromal cells in intestinal-type gastric adenocarcinoma progression. Moreover, invasive intestinal-type gastric adenocarcinoma differs from non-invasive one by the increased KRAS gene mRNA expression, that correlates with the increased levels of EGFR and HER-2/neu expression, and also by the greater correlation between the KRAS gene mRNA and HER-2/neu expression levels. Thus, high KRAS activity and activating signals of functionally related growth factors are maximally realized at invasive stage of the carcinoma progression.
