Prognostic Molecular and Biological Characteristics of Phyllodes Tumors of the Breast.

Prognosis for some histological variants of a rare breast disease, phyllodes tumors, is evaluated. The prognostic potential of some molecular biological factors significantly correlating with breast cancer prognosis is evaluated on a unique clinical material (244 cases with benign, intermediate, and malignant phyllodes tumors). The development of benign phyllodes tumor relapse directly correlated with the number of G0/1-phase cells and inversely correlated with the number of cells in the G2+M and S phases. The level of steroid hormone receptors in phyllodes tumors cannot serve as a prognostic marker predicting the disease course. The presence of somatic mutations of TP53 gene and loss of heterozygosity of specific intragenic loci in the tumor correlate with the development of disease relapse (p<0.05).

The expression and DNA-binding activity of NF-κB nuclear transcription factor in the tumors of patients with breast cancer.

The content and DNA-binding activity of NF-κB nuclear transcription factor subunit p65 (NF-κBp65) were evaluated by quantitative enzyme immunoassay in tumors and histologically intact tissues of 119 patients with breast cancer. DNA-binding activity of NF-κBp65 in the tumors was higher than in adjacent tissue in 97% cases. This elevation was paralleled by an increase in total protein content in the majority of cases. No significant relationship of the parameter with the disease stage, tumor size and histology, and degree of lymph node involvement was detected. However, the content of NF-κBp65 in tumors of malignancy degree III was significantly higher than in tumors of malignancy degree II. An increase in total expression of NF-κBp65 protein was found in HER-2+ tumors. This increase was not related to steroid hormone receptor status and was not paralleled by elevation of DNA-binding activity, which was maximum in tumors with the "triple negative" receptor status (RE-RP-HER-2-).

Soluble fragment of HER2/neu receptor in the serum of patients with breast cancer with different levels of this protein expression in the tumor.

Serum level of soluble HER2/neu in patients with tumors characterized by high expression of this protein (2+/3+ according to immunohistochemical analysis) was significantly higher than in patients with low expression of HER2/neu and in women with benign diseases of the mammary glands. The level of HER2/neu in the serum decreased after removal of the primary tumor in the majority of patients.

Regulation of phospholipid turnover by steroid hormones in endometrial carcinoma and breast cancer cells.

To study the early effects of steroid hormones on cells we investigated the influence of the sex steroids and tamoxifen on phospholipid turnover in endometrial carcinoma and breast cancer cells. Studies were performed on 19 human uterine adenocarcinomas and 29 breast cancer tumors. Progesterone in a final concentration of 10(-7) mol/l caused a twofold decrease of 32P incorporation into phospholipids (phosphatidylcholine and phosphoinositides) in 85% of the uterine adenocarcinomas where the progesterone receptor (PR) content was more than 100 nmol/kg and only in 30% of the tumors where the PR content was less than 100 nmol/kg. Treatment of the cells with 10(-8) mol/l 17 beta-estradiol or 10(-8) mol/l epidermal growth factor led to an increase in 32P incorporation into phospholipids. Analysis of the hormonal responsiveness of 29 human breast cancers showed that 17 beta-estradiol increased 32P incorporation into phospholipids in 47% of the tumors where the estradiol receptor (ER) content was more than 10 nmol/kg and in 21% of the receptor-negative tumors (ER < 10 nmol/kg) The results show that phospholipid turnover in uterine and breast cells can be regulated by sex steroids. Treatment of the breast cancer cells with the antiestrogen tamoxifen (10(-6) mol/l) led to an increase of 32P incorporation into phosphoinositides and a decrease of 32P incorporation into phosphatidylcholine. Addition of an activator of protein kinase C, i.e. 2 x 10(-7) mol/l 12-0-tetradecanoylphorbol-13-acetate, weakened the inhibitory effect of tamoxifen on phosphatidylcholine turnover. These findings suggest that tamoxifen action can be mediated via an alteration of the growth signal transducing system.

Trepanobiopsy as a tool for the study of the influence of presurgical treatment on the steroid receptor status of advanced breast cancer.

Estrogen, progesterone and glucocorticoid receptors were determined in samples obtained by trepanobiopsy before treatment and in surgical material following chemo- or radiotherapy in 131 Stage III a, b, c breast cancer patients. The levels and distribution of the receptors in bioptates coincided with the data obtained earlier for the surgical material from patients, who didn't receive presurgical therapy. It is concluded that breast tumor trepanobioptates may be used for the determination of tumor receptor status. Radiotherapy affected the level and frequency of occurrence of steroid hormone receptors. The degree of variations depended on the dosage of irradiation and after exposure period. After presurgical chemotherapy the percent of receptor-positive tumors increased.