Relationship between Supernatant Cytokines and Expression of Epithelial-Mesenchymal Transition Markers in Biopsy Samples of Invasive Breast Carcinoma of No Special Type with Lymphatic Spread of Metastasis

Abstract

The relationship between the content of supernatant cytokines and the immune histochemical (IHC) expression of epithelial-mesenchymal transition (EMT) markers was studied in biopsy samples of invasive breast carcinoma of no special type (IBC-NST) from patients with and without lymphatic spread of metastases (group II and group I, respectively). The concentrations of TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, MCP-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, and IL-1Ra, as well as the immunohistochemical (IHC) expression of EMT markers cadherin-E (CDH1), β-1 integrin (CD29) and type II collagen (CII) were assayed. Results have shown that the patients of these groups statistically significantly differed by spontaneous production of IL-18 and G-CSF, and by the index of the polyclonal activator influence (IPAI) on G-CSF production. The study of relationships between supernatant cytokine production and the IHC expression by biopsy samples revealed correlations between the parameter of CII expression in the tumor tissue and the cytokine production by tumor biopsy specimens; these correlation links were typical for all IBC-NST patients, while correlation links (both direct and reverse ones) between CDH1, CD29, and cytokine production varied in groups of patients with and without lymphatic spread of metastases. The study revealed the features of the correlation links between the cytokine production by the tumor, its microenvironment and the IHC expression of EMT markers in IBC-NST patients with and without lymphatic spread of metastasis.