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 very important roles in the pathogenesis and development of various sex steroid-dependent neoplasms including breast and endometrial carcinoma. 17β-Hydroxysteroid dehydrogenase (17β-HSD) isozymes catalyze the interconversion of estradiol (E₂) and estrone (E), and thereby serve to modulate the tissue levels of bioactive E₂. 17β-HSD type 1 primarily catalyzes the reduction of E₁ to E₂, whereas 17β-HSD type 2 primarily catalyzes the oxidation of E₂ to E₁. In the human breast and its disorders, 17β-HSD type 1 is expressed in proliferative diseases without atypia, atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. 17β-HSD type 2 is not detected in any of the lesions. In addition, 17β-HSD type 1 coexpression is significantly correlated with estrogen receptor status in invasive ductal carcinoma cases. These results indicate that breast carcinoma can effectively convert E₁, produced as a result of in situ aromatization, to E₂, a biologically potent estrogen, and exerts estrogenic actions on tumor cells through the estrogen receptor. On the other hand, in the human endometrium, 17β-HSD type 2 is expressed, but not 17β-HSD type 1. 17β-HSD type 2 is expressed in the secretory phase but not in any proliferative phase in the endometrial mucosa. The enzyme is expressed in 75% of endometrial hyperplasias and 37% of carcinoma cases. In endometrial carcinoma cases, a significant inverse correlation has been detected between 17β-HSD type 2 immunoreactivity and age (p < 0.02). These results indicate that oxidation of E₂ to E₁ is dominant in endometrial carcinoma, 17β-HSD types 1 and 2 play an important role in the regulation of in situ estrogen production in breast and endometrial carcinoma. Copyright (C) 2000 S. Karger AG, Basel.