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

• Main Authors: V. A. Tumanskiy, T. A. Khrystenko
• Format: Article
• Language: English
• Published: Zaporozhye State Medical University 2017-08-01
• Series: Patologìâ
• Subjects: gastric cancer; adenocarcinoma; growth factor receptors; cell proliferation; apoptosis
• Online Access: http://pat.zsmu.edu.ua/article/view/109250/105906
• ISSN: 2306-8027; 2310-1237

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.