[Expression of markers of epithelial-mesenchymal transition in breast cancer]. / Ekspressiya markerov epitelial'no-mezenkhimal'nogo perekhoda pri rake molochnoi zhelezy.

OBJECTIVE: To study of the expression of epithelial-mesenchymal transition markers in various molecular subtypes of cancer and in benign breast diseases with different risks of malignant transformation. MATERIAL AND METHODS: An immunohistochemical study of the expression of E-cadherin, collagen II, integrin 1ß, cyclin D1 was carried out in breast tissue samples: 58 with invasive breast carcinoma of no special type and 17 with benign breast diseases with a high and low risk of malignant transformation. RESULTS: Patients with a triple negative molecular subtype are characterized by lower expression of collagen II compared with individuals with luminal A and B+ subtypes. A distinctive feature of patients with the HER2+ subtype was increased expression of cyclin D1 compared with the luminal A subtype, and in patients with the luminal B+ subtype, the expression of integrin 1ß is higher than in the luminal B- and HER2+ subtypes. The expression of cyclin D1 in patients of both groups with benign diseases was lower than in all groups with invasive carcinoma, but at the same time, in patients with a low risk of malignant transformation, the expression of cyclin D1 was higher than in those with an increased risk. CONCLUSION: The study revealed the relationship between the expression of markers and molecular subtypes of breast tumors, in addition, some patients with benign diseases were found who need further more careful monitoring and may be at risk for the development of malignancy.

Influence of HLDF Differentiation Factor on Nonspecific Invasive Breast Carcinoma in vitro.

The study was carried out on samples of invasive breast carcinoma of no special type from 36 patients aged 48.0 to 62.8 years. The effect of HLDF on nonspecific invasive breast carcinoma was a decrease in the relative content of low-differentiated cells and an increase in the relative content of highly differentiated cells. HLDF did not have a cytotoxic effect leading to the death of low-differentiated cells but promoted promotes the acquisition of a higher degree of differentiation by them. A more pronounced effect of HLDF was observed in more aggressive metastasizing forms of neoplasia, which allows us to consider this differentiation factor as a candidate for use in the differentiation therapy of malignant neoplasms.

[Proteins and immunohistochemical markers of breast diseases]. / Belkovye i immunogistokhimicheskie markery zabolevanii molochnoi zhelezy.

In this work, we have compared malignant and non-malignant diseases of the mammary gland using 8 proteins: HRG, MUC1, PAI-1, HSP90αA1, CDH1, ERα, PGR and IL-12. Their concentrations in the supernatants of blood cells and breast biopsies were compared in terms of spontaneous production, induced by a polyclonal activator and after exposure to biopsy samples of the HLDF differentiation factor, as well as the indices of the effect of the polyclonal activator and HLDF on the protein production. In addition, the correlation relationships of the above indicators with the expression of markers of the epithelial-mesenchymal transition: collagen type II (CII), ß-1 integrin (CD29) and cadherin-E (CDH1) were studied. The study revealed statistically significant differences in the concentration of HRG in the supernatant of blood cells, IL-12 during spontaneous production by biopsy specimens, PGR production of biopsy specimens induced by the polyclonal activator, CDH1 and IL-12 production biopsy specimens exposed to HLDF. According to the influence index of the polyclonal activator and HLDF, statistically significant differences were found for CDH1production. Comparison of non-specific invasive carcinoma biopsy specimens and non-malignant breast diseases by means of the markers of the epithelial-mesenchymal transition revealed statistically significant differences in CD29 expression and the lack of differences in the expression of CDH1 and CII. This indicates the presence of cell atypia in samples of non-malignant breast diseases; it is confirmed by the recognized correlation between the production of certain proteins and the expression of the epithelial-mesenchymal transition markers.

[Relationship between supernatant cytokines and expression of markers of epitelial-mesenchymal transition of invasive breast carcinoma of non-specific lymphynosis type]. / Vzaimosviaz' mezhdu tsitokinami supernatantov i ékspressiei markerov épitelial'no-mezenkhimal'nogo perekhoda bioptatov invazivnoi kartsinomy molochnoi zhelezy nespetsificheskogo tipa pri limfogennom metastazirovanii.

The relationship between the content of supernatant cytokines and the expression of non-specific type of markers of epithelial-mesenchymal transition markers in the presence (group II) and the absence of lymphogenous metastasis (group I) were studied in biopsy specimens of mammary invasive breast carcinoma. 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-1ß and IL-1Ra, as well as the expression of immunohistochemical (IHC) markers of the epithelial-mesenchymal transition - cadherin-E (CDH1), ß-1 integrin (CD29) and type II collagen (CII) were assayed. Results have shown that patients of these groups statistically significantly differed in spontaneous production of IL-18 and G-CSF, in terms of the index of the effect of the polyclonal activator on G-CSF production. There was a correlation between the parameter of CII expression in tumor tissue and the production of cytokines by tumor biopsy specimens; it was characteristic of all patients with invasive carcinoma of a non-specific type, and correlations, both direct and reverse between the expression indices of CDH1, CD29 and cytokine production varied depending on the presence or the absence of lymphogenous metastasis. The study revealed the features of the correlation between the production of cytokines by the tumor, its microenvironment and the expression of IHC markers of the epithelial-mesenchymal transition in patients with invasive non-specific breast carcinoma in the presence and absence of lymphogenous metastasis.

[Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type]. / Produktsiia tsitokinov immunokompetentnymi kletkami krovi, opukhol'iu i ee mikrookruzheniem, osobennosti sostoianiia vnekletochnogo matriksa u bol'nykh invazivnoi kartsinomoi molochnoi zhelezy nespetsificheskogo tipa.

The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ß, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 was determined by the solid-phase enzyme-linked immunosorbent assay. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1ß; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.