The features of transcriptional activity of K-RAS gene and expression of ErbB family receptors in intestinal-type gastric adenocarcinoma

Abstract

Aim – to study the features of expression of the K-RAS gene mRNA and the ErbB family growth receptors (EGFR and HER-2/neu) by the tumor cells of the intestinal-type gastric adenocarcinoma, and also their relations to the processes of cell proliferation and apoptosis.Materials and methods. Pathohistological, immunohistochemical and molecular-genetic studies of the intestinal-type gastric adenocarcinoma from 30 patients (the age ranged from 49 to 86 years) and 10 samples of the normal gastric mucosa were performed.Results. It has been established that intestinal-type gastric adenocarcinoma is characterized by the elevated level of expression of the K-RAS gene mRNA [Me = 3.62 (0.57; 5.87)]. There is the inverse weak correlation between the elevated expression level of the K-RAS gene mRNA and the decrease of the histological differentiation degree of the tumor from G3 to G1 (r = -0.36). In 100 % of the intestinal-type gastric adenocarcinomas, that were investigated, membrane expression of the EGFR and HER-2/neu receptors was detected. Herewith the intense expression of the EGFR (++/+++) occurs in 76.66 % of the adenocarcinomas, while the HER2 positive status (+++) occurs in 46.66 % of the adenocarcinomas. There is the direct strong correlation between the expression levels of the EGFR and HER2/neu markers by the tumor cells (r = 0.80), the direct medium correlation between the expression levels of the EGFR and Ki-67 markers (r = 0.53), and the direct medium correlation between the expression levels of the EGFR marker and K-RAS gene mRNA (r = 0.57). There are no correlations between the levels of expression of the apoptosis markers (p53 and caspase-3), EGFR and HER2/neu receptors, as well as the expression level of the K-RAS gene mRNA by the tumor cells of intestinal-type gastric adenocarcinoma.Conclusions. These data suggest that the increasing of the expression levels of EGFR and HER2/neu receptors by the tumor cells of intestinal-type gastric adenocarcinoma leads to the activation of transcription and translation of the K-RAS gene, followed by the activation of the ERK-signaling pathway that realizes the proliferative potential of the tumor cells. The examination of ErbB–state of the intestinal-type gastric adenocarcinoma is expediently for the individual target-treatment selection.