Медицинская иммунология (Aug 2019)
ASSOCIATION OF TUMOR CELL DIFFERENTIATION WITH CYTOKINE-PRODUCING RESERVE IN BREAST CANCER LUMINAL AND NON-LUMINAL SUBTYPES.
Abstract
There is a direct association between the functional, morphologic and biochemical atypism of cellular tumor expression and malignancy. Five moleclular-genetic subtypes of breast cancer are established. According to the literature the most aggressive course is known to be characterized by non-luminal subtypes mostly triple negative breast cancer. The aim of this research is to determine the association between the percentage of the cells having various differentiation with cytokine production by breast cancer bioptates in both luminal and non-luminal breast cancer subtypes. Bioptates of 49 women with the invasive breast carcinoma of non-specific type, with the average age being 59 years were used as the material for the research. The patients were divided into three groups according to the molecular-genetic subtype of cancer. Group I includes 12 patients with luminal A subtype, group II – 30 patients with luminal B subtype and group III includes 7 those with non-luminal one. To determine the bioptate cytokine-producing reserve the production of cytokines IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNFα, IFNγ, G-CSF, GM-CSF, VEGF-А, MCP-1 by both spontaneous and stimulated polyclonal activators were investigated. Bioptate cytokine-producing reserve was shown by the index of the polyclonic activators effect. The percentage of the cells having various differentiation in the non-specific type of invasive carcinoma bioptates was assesed by light microscopy taking into consideration Nottingham grade system. It is established that the patients with non-luminal subtype have higher both spontaneous and stimulated polyclonal activators production of IL-IRa compared with the women from the I and II groups. Groups I and III were characterized by higher spontaneous IL-10 and G-CSF production compared with that of group II. Studying the effect of polyclonic activators on the production on G-CSF in group I and III it was shown the production of this cytokine to be higher than that in group II. Index of the polyclonic activators effect on the production of G-CSF and GM-CSF was lower in group III than that in group II. It means that the reserve of this cytocine production in patients with non-luminal breast cancer subtypes is completed. And vice versa, the index of the polyclonic activators effect on the production of VEGF-A increases in group III compared with that of group II. Comparing cytokine production between luminal breast cancer subtypes (group I and II) true differences in spontaneous MCP-1 production and stimulated production of IL-10, G-CSF as well as in index of the polyclonic activators effect on the production of IL-2, IL-17, IFNγ were revealed. While assesing the percentage of low-differentiated cells much higher percentage was shown compared with those of the others. Definite correlations were revealed analyzing the association between the percentage of cells having various differentiation with cytokine production. Negative association between the spontaneous production of VEGF-А и IL-6 and percentage of low-differentiated cells, as well as positive association between percentage of high-differentiated cells and production IFNγ by stimulated polyclonal activators was established. Assesing the index of polyclonal activator effect on the production of G-CSF and high-differentiated cells percentage the negative association was found out. There were revealed 5 variants of association between spontaneous production of IL-2, IL18, IL-Iβ, IL-IRa, G-CSF and the percentage of low- and moderate-differentiated cells, 5 variants of association between stimulated production of IL-2, IL-18, GM-CSF and the percentage of moderate- and low-differentiated cells in group II. Assesing the index of polyclonal activator effect in this patient group positive association between the percentage of moderate- differentiated cells and IL8, IL-IRa и G-CSF was found out. The negative association was determined between spontaneous production of IL-Iβ and the percentage of moderate- differentiated cells, 3 negative associations between stimulated production of IL-6, IL-8 и IFNγ with the percentage of moderate- differentiated cells and negative correlation between the index of polyclonal activator effect on IL-17 and the percentage of moderate- differentiated cells in group III. The analysis of ROC-curves showed good quality and optimal level of cytokine concentration and the percentage of low- differentiated cells, that could predict the presence of unfavorable non-luminal breast cancer subtypes in the best way. On the data obtained, we can make a conclusion that cytokine-producing reserve is connected with the cellular differentiation and depends on tumor molecular-genetic subtype.
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