Association of tumor cell differentiation with cytokine-producing reserve in luminal and nonluminal subtypes of breast cancer

There is a direct association between the functional, morphologic and biochemical atypic features of cellular tumor expression and malignancy. Five molecular-genetic subtypes of breast cancer are recognized. The most aggressive course is known to be characterized by non-luminal subtypes, in particular, a triplenegative breast cancer. The aim of this research is to determine the association between the percentage of the cells showing distinct differentiation types, and 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 nonspecific type, at the average age of 59 years, were used as the material for the study. The patients were divided into three groups according to the molecular-genetic subtype of cancer. Group I included patients with luminal subtype A, group II – with luminal B and group III – with non-luminal subtypes of breast cancer. Spontaneous and in vitro stimulated by polyclonal activators production of cytokines was evaluated. The level of cytokineproducing reserve by the biopsy specimens was expressed as the influence index of polyclonal activators, due to its accuracy, thus making it possible to avoid errors due to the similar sizes of bioptates from each patient and their incubation conditions. The percentage of tumor cells of varying degrees of differentiation in the samples was assessed using light microscopy by means of the Nottingham grading system. When assessing spontaneous and stimulated production of cytokines, as well as degree of cell differentiation of tumor samples, direct and reverse correlations were revealed between the study groups. The most important parameter was the influence index of the polyclonal activator which characterized production of IL-10 and VEGF-A by the bioptates. Therefore, we can provide personalized information for each patient, in particular, for these two cytokines, even before starting the treatment.The analysis of ROC-curves showed good quality and optimal level of cytokine concentration and percentage of low-differentiated cells. This approach could predict the presence of unfavorable non-luminal breast cancer subtypes in the best way. In general, we can make a conclusion that cytokine-producing reserve is connected with cellular differentiation and depends on molecular-genetic subtype of the tumor.

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