Histological evaluation of in vitro responses of endometrial adenocarcinoma to progestins and their relation to progesterone receptor levels.

In vitro responsiveness of endometrial adenocarcinoma to progestins was evaluated histologically by incubation of tissue fragments in medium containing 10(-6) M medroxyprogesterone acetate. In a series of 19 experiments, formation of sub- and supranuclear vacuoles, which reflects accumulation of glycogen in response to medroxyprogesterone acetate added to the medium, was observed in well-preserved glandular epithelial cells only when the level of cytosolic progesterone receptor was above 300 fmol/mg protein. Previously, we have reported similar results obtained in in vivo experiments. The present findings suggest that simple organ culture and histological procedures can be used to identify specimens of endometrial cancer that have functional progesterone receptors and are capable of responding to progestins. They also indicate that levels of progesterone receptor required to obtain responses to progestins are considerably higher than those necessary for analytical detection and that therefore the quantity and not merely the detectability of progesterone receptors must be taken into consideration for the prediction of responses to progestins. In addition, in vitro responses to progestins may indicate the presence in endometrial cancer tissue of functional estrogen receptors and potential responsiveness to antiestrogens, since estrogen stimulation appears to be needed for the synthesis of progesterone receptors.