Epithelial – mesenchymal transition markers, proliferation markers, and cytokine secretion in breast tissue in malignant and benign breast diseases

Abstract

Aim. To develop methodological grounds for assessing the probability of breast malignancy in patients with noncancerous breast diseases (NCBD) by the following parameters: expression of markers of epithelial – mesenchymal transition (EMT) and proliferation and production of cytokines by samples of the breast tissue.Materials and methods. In breast samples (BS) of patients with invasive carcinoma of no special type (ICNT) and patients with NCBD, immunohistochemistry was used to determine the expression of E-cadherin (CDH1), integrin β1 (CD29), type II collagen (CII), and proliferation of Ki-67. Using the enzyme-linked immunosorbent assay, concentrations of interleukin (IL)-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, tumor necrosis factor (TNF)α, interferon (IFN)γ, granulocyte colony-stimulating factor (G-CSF), granulocyte – macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF)-A, and monocyte chemoattractant protein (MCP)-1 were determined in the supernatant of the cultured breast tissue samples.Results. It was shown that ICNT and NCBD differ in the expression of E-cadherin, CD29, Ki-67, and the production of IL-2, IL-4, IL-6, IL-17, IL-18, IL-1Ra, TNFα, IFNγ, and MCP-1. The ROC analysis found that the models characterizing the differences between the ICNT and NCBD samples were formed by the parameters of CD29 and Ki-67 expression and IL-17, IL-18, TNFα, VEGF-A, and MCP1 production. The neural network analysis revealed that CD29, IL-1Ra, TNFα, and VEGF-A had the greatest normalized importance for assessing the differences between the ICNT and NCBD samples. Clustering of the combined database of patients with NCBD and ICNT by the expression of E-cadherin, CD29, Ki-67 and by the production of IL-17, IL-18, TNFα, MCP-1, and VEGF-A resulted in a cluster which includes the parameters of 94.1% of patients with NCBD. The parameters of less than 10% of patients with NCBD who fell into other clusters practically coincided with the studied parameters of the ICNT group, which suggests that these patients may form a risk group with the malignancy probability of more than 90%.Conclusion. The data obtained made it possible to develop methodological grounds for assessing the likelihood of breast malignancy in patients with NCBD.