The correlation between the response to progestogen treatment and the expression of progesterone receptor B and 17beta-hydroxysteroid dehydrogenase type 2 in human endometrial carcinoma.

Abstract

In situ metabolism and synthesis of oestrogens are considered to play important roles in the pathogenesis and development of human endometrial endometrioid adenocarcinoma. Approximately 3-5% of patients with these neoplasms are under age 40, some of whom have been treated with progestogen alone as a primary therapy for both atypical endometrial hyperplasia and adenocarcinoma in order to preserve their fertility. Medroxyprogesterone acetate (MPA) has been used extensively in the treatment of both breast and endometrial disorders as an endocrine therapy. However, details of the alterations of in situ oestrogen metabolism following progestogen treatment have yet to be fully elucidated. In this study we examined the immunolocalization of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) types 1 and 2, oestrogen receptor (ER), progesterone receptor (PR)A + PRB, PRB, and Ki67 in progestogen-treated endometrial endometrioid adenocarcinoma (16 cases). We compared our findings both prior to and following treatment. These findings were then correlated with the treatment outcome of individual patients in order to elucidate factors associated with the response to treatment. 17beta-HSD type 2 immunoreactivity was detected in 8/16 cases examined, whereas 17beta-HSD type 1 immunoreactivity was undetected in all cases examined. 17beta-HSD type 2 positive immunostaining, PRA + PRB labelling index (LI), and PRB/PRA + PRB ratio were all significantly higher in cases responding to the treatment than in those not responding. There were no significant correlations between responsive and nonresponsive cases for positive 17beta-HSD type 1 immunostaining, Ki67 LI, ER LI and age. There were no significant differences in the positive immunostaining for 17beta-HSD types 1 and 2, Ki67 LI, ER LI, PRA + PRB LI, age and PRB/PRA + PRB ratio between specimens taken prior to and following progestogen treatment. These results suggest that in situ abundance of 17beta-HSD type 2 and PR, especially PRB, can predict the possible response of patients with endometrial carcinoma to progestogen treatment.