Relationship between supernatant cytokines and expression of markers of epitelial-mesenchymal transition of invasive breast carcinoma of non-specific lymphynosis type

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-1β and IL-1Ra, as well as the expression of immunohistochemical (IHC) markers of the epithelial-mesenchymal transition - cadherin-E (CDH1), β-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.Izuchena vzaimosviaz' mezhdu soderzhaniem tsitokinov supernatantov i ékspressieĭ v bioptatakh invazivnoĭ kartsinomy molochnoĭ zhelezy nespetsificheskogo tipa markerov épitelial'no-mezenkhimal'nogo perekhoda pri nalichii (II gruppa) i otsutstvii (I gruppa) limfogennogo metastazirovaniia. Opredeliali kontsentratsiiu 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 i IL-1Ra, a takzhe ékspressiiu immuno-gistokhimicheskikh (IGKh) markerov épitelial'no-mezenkhimal'nogo perekhoda – kadgerina-E (CDH1), β-1-integrina (CD29) i kollagena II tipa (CII). Po rezul'tatam issledovaniia patsienty étikh grupp statisticheski znachimo otlichalis' po spontannoĭ produktsii IL-18 i G-CSF, po indeksu vliianiia poliklonal'nogo aktivatora na produktsiiu G-CSF. Pri izuchenii vzaimosviazi mezhdu produktsieĭ tsitokinov supernatantami i ékspressieĭ v nikh IGKh markerov ustanovleno, chto korreliatsionnye sviazi mezhdu pokazatelem ékspressii CII v tkani opukholi i produktsieĭ tsitokinov bioptatami opukholi kharakterny dlia vsekh patsientov s invazivnoĭ kartsinomoĭ nespetsificheskogo tipa, a korreliatsionnye sviazi, kak priamye, tak i obratnye mezhdu pokazateliami ékspressii CDH1, CD29 i produktsieĭ tsitokinov, razlichalis' v zavisimosti ot nalichiia ili otsutstviia limfogennogo metastazirovaniia. Provedennoe issledovanie pozvolilo vyiavit' osobennosti korreliatsionnykh sviazeĭ mezhdu produktsieĭ tsitokinov opukhol'iu, ee mikrookruzheniem i ékspressieĭ IGKh – markerov épitelial'no-mezenkhimal'nogo perekhoda u patsientov s invazivnoĭ kartsinomoĭ molochnoĭ zhelezy nespetsificheskogo tipa pri nalichii i otsutstvii limfogennogo metastazirovaniia.