[Progenotoxic shift in mammary adipose tissue (adipogenotoxicosis): association with clinical and biological characteristics of breast cancer].

The study is concerned with identification of a relationship between levels of production and accumulation of compounds capable of hormonal and progenotoxic effects in mammary fat, on the one hand, and characteristics of tumor tissue in breast cancer, on the other. Mammary fat was sampled at a distance of 1.5-2 cm from tumor edge (79 pts.). Case histories were used to provide data on clinical stage, size, grade and regional lymph node involvement. Levels were assayed of leptin, adiponectin, tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO), thiobarbiturate-reactive products (TBRP) and DNA oxidative damage marker (8-OH-dG) from 4hr-incubates of fat tissue culture. Mammary fat aromatase was assayed by radiometrical means while macrophage-assisted fat infiltration (CD68) and estrogen-4-hydroxylase (CYP1B1) expression were evaluated immunohistochemically. Radio-competitive and immunohistochemical methods were used to assay estrogen (ER) and progesterone (PR) receptor levels in tumor and tumor-related expression of cytokeratins 5/6 ("basal") and 7/8 ("luminal" epithelium), respectively. As far as hormonal properties of mammary fat were concerned, there were direct correlations between aromatase concentration, on the one hand, and tumor stage and size, on the other, and adiponectin secretion and CK7 expression in tumor. Besides, an inverse correlation was found between mammary fat-mediated release of leptin and adiponectin, on the one hand, and stage and regional lymph node involvement, on the other. The following main relationships were identified by comparison of the clinico-biological characteristics of tumor and markers of proinflammatory/progenotoxic properties of mammary adipose tissue: tendency toward direct correlation with IL-6 and 8-OH-dG in fat (tumor progress stage); direct correlation with TNF-alpha secretion rate (malignancy grade); lymph node involvement--tendency toward direct correlation with NO generation; CK5 expression in tumor--tendency toward direct correlation with 8-OH-dG, TBRP and CD68 fat infiltration; CK7 expression in tumor--tendency toward inverse correlation with NO generation in adipose tissue; ER-negative phenotype of tumor--tendency toward higher generation of TBRP, NO and TNF/leptin in fat. Hence, shift toward predominance of proinflammatory/progenotoxic properties of mammary adipose tissue (adipogenotoxicosis) is associated with signs of less favorable course of tumor process in the mammary gland which calls for working out adequate measures.