Immunohistochemical analysis of 17β-hydroxysteroid dehydrogenase isozymes in human ovarian surface epithelium and epithelial ovarian carcinoma

Abstract

Epidemiological studies have indicated a relationship between gonadal steroid hormones, primarily estrogens, and epithelial ovarian carcinoma. In situ estrogen metabolism and synthesis have been considered to play important roles in the development of the progression of epithelial ovarian carcinoma. 17β-Hydroxysteroid dehydrogenases (17β-HSDs) are a group of intracellular isozymes catalyzing interconversions between estradiol (E2) and estrone (E1). In the last step of steroidogenesis, 17β-HSD type 1 catalyzes the 17β-reduction and produces E2 from E1. The oxidative enzymes known as types 2, 4, and 8 are potent estrogen-inactivating enzymes that convert E2 to E1. Here we report the immunoexpression of 17β-HSD types 1, 2, 4, and 8 in normal human ovarian surface epithelium (OSE) and epithelial ovarian carcinoma. For this study, novel polyclonal antibodies were generated against each type of 17β-HSD. Of the six normal OSE cases investigated, 17β-HSD types 1, 4, and 8, but not type 2, were found in the cytoplasm of epithelial cells. In 58 cases of epithelial ovarian carcinoma (45 serous, 4 endometrioid, 4 mucinous, and 5 clear cell), estrogen-inactivating 17β-HSDs were commonly found (type 2, 84.5%; type 4, 82.8%; type 8, 86.2%), whereas type 1 was detected in only 10 cases (17.2%). These results indicate that 17β-HSDs may be involved in the protective and/or suppressive effects against the estrogen-dependent proliferation of epithelial ovarian carcinoma.