The Relationship Between Cytokine Production, CSF2RA, and IL1R2 Expression in Mammary Adenocarcinoma, Tumor Histopathological Parameters, and Lymph Node Metastasis

Abstract

Objective: The aim of this study was to evaluate the relationship between cytokine production, GM-CSF receptor (CSF2RA), and IL-1 receptor (IL1R2) expression in mammary adenocarcinoma and their association with it histopathological parameters and lymph node metastasis. Methods: We analyzed tumor biopsy samples (cultured in vitro) from 50 women (aged 43-75) with invasive ductal mammary adenocarcinomas. Enzyme-linked immunosorbent assay method the concentrations of interleukin 2, interleukin 6, interleukin 8, interleukin 10, interleukin 17, interleukin 18, interleukin 1β, interleukin 1Ra, tumor necrosis factor α, interferon γ, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, and vascular endothelial growth factor A were determined in culture supernatants. The expression of CSF2RA and IL1R2 in tumor biopsy was evaluated by immunohistochemical method. Results: We showed that the “cytokine profile” of a tumor (the ability of tumor cells and its microenvironment to produce different cytokines) is very individual. It has been shown that the features of the cytokine profile of the mammary adenocarcinoma are important for the formation and realization of the metastatic potential of the mammary adenocarcinoma. We found correlations between some histopathological parameters of mammary adenocarcinoma and coefficients KGM-CSF/CSF2RA and KIL-1β/IL1R2, which are the ratios of concentrations of granulocyte macrophage colony-stimulating factor and interleukin -1β to expression of CSF2RA and IL1R2, respectively. KGM-CSF/CSF2RA positively correlated with highly differentiated cells, and KIL-1β/IL1R2 positively correlated with the number of mitoses, poorly differentiated cells, and a number of lymph nodes with metastases. KGM-CSF/CSF2RA positively correlated with the concentrations of interleukin 6, interleukin 8, interleukin 1Ra, and granulocyte colony-stimulating factor. KIL-1β/IL1R2 positively correlated with concentrations of interleukin 1β and interferon γ and negative correlated with the concentrations of vascular endothelial growth factor A and tumor necrosis factor α. It is shown that KIL-1β/IL1R2 can be considered as a prognostic indicator predicting the probability of mammary adenocarcinoma metastasis to regional lymph nodes. Conclusions: The ratios of granulocyte macrophage colony-stimulating factor and interleukin 1β cytokines, produced in tumor, to the expression of CSF2RA and IL1R2 depend on levels of interleukin 6, interleukin 8, tumor necrosis factor α, interferon γ, granulocyte colony-stimulating factor, and vascular endothelial growth factor A and are important factors affecting the progression and metastasis of the breast cancer.