17-Beta-hydroxysteroid dehydrogenase in human breast and endometrial carcinoma - A new development in intracrinology

Intratumoral metabolism and synthesis of estrogens are considered to play v ery important roles in the pathogenesis and development of various sex ster oid-dependent neoplasms including breast and endometrial carcinoma. 17 beta -Hydroxysteroid dehydrogenase (17 beta -HSD) isozymes catalyze the interco nversion of estradiol (E-2) and estrone (E-1), and thereby serve to modulat e the tissue levels of bioactive E-2. 17 beta -HSD type 1 primarily catalyz es the reduction of E-1 to E-2, whereas 17 beta -HSD type 2 primarily catal yzes the oxidation of E-2 to E-1. In the human breast and its disorders, 17 beta -HSD type 1 is expressed in proliferative diseases without atypia, at ypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal car cinoma. 17 beta -HSD type 2 is not detected in any of the lesions. In addit ion, 17 beta -HSD type 1 coexpression is significantly correlated with estr ogen receptor status in invasive ductal carcinoma cases. These results indi cate that breast carcinoma can effectively convert E-1, produced as a resul t of in situ aromatization, to E-2, a biologically potent estrogen, and exe rts estrogenic actions on tumor cells through the estrogen receptor. On the other hand, in the human endometrium, 17 beta -HSD type 2 is expressed, bu t not 17 beta -HSD type 1. 17 beta -HSD type 2 is expressed in the secretor y phase but not in any proliferative phase in the endometrial mucosa. The e nzyme is expressed in 75% of endometrial hyperplasias and 37% of carcinoma cases. In endometrial carcinoma cases, a significant inverse correlation ha s been detected between 17 beta -HSD type 2 immunoreactivity and age (p < 0 .02). These results indicate that oxidation of E-2 to E-1 is dominant in en dometrial carcinoma, 17<beta>-HSD types 1 and 2 play an important role in t he regulation of in situ estrogen production in breast and endometrial carc inoma. Copyright (C) 2000 S. Karger AG, Basel.