Estradiol, progesterone and steroid receptors. Benign cycling versus malignant non cycling cells

Levels of estradiol and progesterone from blood together with oestrogen (ER) and progesterone receptors (PgR) from breast tissue were studied from a total of 2500 data bank cases of breast neoplastic disease. We report here, 340 premenopausal women with recorded menstrual cycle data which enabled the study of the effect of peripheral hormone variation on ER and PgR with respect to cycle phase. The findings were also correlated with 30 immunohistochemical specimens. In the specimens with benign neoplasm (141 cases, age 28 +/- 18 years) the ER levels were low (9.2+/-9.4 fmol/mg protein) as in normal breast tissue, whereas PgR levels were high ( 76+/-102.4 fmol/mg protein). Both ER and PgR levels decreased in association with the peak of blood progesterone of the early secretory phase. In the 15 cases of benign neoplasm from the luteinic phase studied by immunohistochemistry there were few ER positive cells (29+/-15%) which were small (265+/-27 pixels) and faintly stained (MOD: 34+/-3UA), while the PgR positive cells were more numerous (79+/-15%), bigger (377+/-70 pixels), strongly stained (MOD: 48+/-5UA), and centrally located in the breast ducts. The differences in size and optical density were statistically significant indicating that both receptors are expressed by different cells. The cell cycle dependence of these differences is discussed. In the series of malignant neoplasms (199 cases, age 41+/-6 years), ER and PgR cytosol levels were both generally high (ER: 38+/-75.9, PgR: 86.6+/-137), and did not show variations due to the menstrual cycle, while blood progesterone, PgR, and the percentage of ER positive cases increased during the menstrual cycle. The 15 malignant cases in the luteinic phase showed, through immunohistochemistry, that size and staining intensities of receptor positive cells were similar to the other 199 cases and were not found to be directly influenced by hormonal activity related to the menstrual cycle. Comparisons between benign and malignant specimens showed significant biochemical and immunohistochemical differences in the degree of ER positivity while, on the contrary, PgR levels were similar.