ESTROGEN-RECEPTORS, PROGESTERONE RECEPTORS, AND CELL-PROLIFERATION INHUMAN BREAST-CANCER

The breast is a target organ for estrogens and progesterone. These hor mones control several functions of the normal and abnormal mammary epi thelium including cell proliferation. Most of the actions of estrogens and progesterone are mediated via specific steroid receptors, and one would expect that proliferating cells should contain estrogen recepto rs (ER) and/or progesterone receptors (PR). However, the correlation b etween receptor expression and cell proliferation is still controversi al. In the present study we have examined 29 human breast cancer sampl es; in 17 of them we evaluated the simultaneous ER and PR localization with that of proliferating cell nuclear antigen (PCNA) and silver-sta ined nucleolar organizer regions (AgNORs) in a cell-by-cell study. We found that in almost 50% of the tumor biopsies examined, the cells exp ressing ER were significantly associated with elevated cell proliferat ion. In another group (38%) there were not significant differences bet ween ER expression and cell proliferation. In only one of the samples (6%) the cells expressing ER showed lower cell proliferation. The stud y also revealed that in 44% of the tumors the PR expressing cells were associated with elevated cell proliferation. In a second group the PR expression was not significantly associated with cell proliferation ( 33% of the cases). Finally, in 22% of the samples the cells carrying P R showed lower cell proliferation. We also detected lower ER immunorea ctivity in 30% of the breast cancer biopsies with one of the monoclona l antibodies against ER (antibody 1D5 directed against the A/B domain) . This group of tumors was PR-negative (or very weakly positive) and h ad high proliferation. The presence of tumors with 'abnormal' ER prote ins and displaying ER/PR significantly associated with elevated cell p roliferation could have implications in human breast cancer treatment.