Progesterone therapy for endometrial carcinoma reduces cell proliferation but does not alter apoptosis.

BACKGROUND: Although the anticancer effects of progesterone therapy for patients with endometrial carcinoma are widely acknowledged, a detailed assessment of the resultant morphologic alterations in tumor tissue kinetics has hitherto been lacking.
METHODS: Biopsy and hysterectomy specimens of 14 endometrial carcinomas (endometrioid-type) before and during progesterone therapy were studied to clarify changes in apoptosis and cell proliferation and their relation to morphologic alterations. The extent of squamous differentiation within tumor lesions was also examined.
RESULTS: In the good-response group, tumor cells took on characteristics of normal endometrial gland cells in the secretory phase. A positive correlation between reduction in the mitotic index and the degree of morphologic alterations during hormone therapy was observed, but the frequency of apoptotic cells did not vary. In both the good-response and poor-response groups, development or enlargement of squamous areas was observed, in comparison with the initial biopsy specimens.
CONCLUSIONS: These results suggest that prolonged progesterone administration can suppress cell proliferation in endometrial carcinomas through tumor cell differentiation without altering apoptosis, resulting in a shift in tissue kinetics toward a relative predominance of cell deletion. In addition, increases in the occurrence of squamous areas within tumors do not always appear to be related to treatment efficacy.