The analyses of 17 beta-hydroxysteroid dehydrogenase isozymes in human endometrial hyperplasia and carcinoma

Intratumoral metabolism and synthesis of estrogens are considered to play v ery important roles in the pathogenesis and development of human endometria l adenocarcinoma. The 17 beta -hydroxysteroid dehydrogenase (17 beta -HSD) isozymes catalyze the interconversion of estradiol (E2)and estrone and ther eby serve to modulate the tissue levels of bioactive E2. To elucidate the p ossible involvement of this enzyme in human endometrial carcinoma, we first examined the expression of 17 beta -HSD type 1 and type 2 in 20 normal cyc ling human endometria, 36 endometrial. hyperplasia, and 46 endometrial endo metrioid adenocarcinoma using immunohistochemistry, and we then studied imm unoreactivity of 17 beta -HSD type 2 using immunoblotting analyses, the act ivity of 17 beta -HSD type 1 and type 2 using thin-layer chromatography and their expression using RT-PCR in endometrial endometrioid adenocarcinoma. We correlated these findings with various clinicopathological parameters to examine the biological significance of 17 beta -HSDs in human endometrial disorders. 17 beta -HSD type 2 immunoreactivity in normal endometrium was p resent in all cases of secretory phase (n = 14), but not in any endometrial mucosa of proliferative phase (n = 6). In addition, 17 beta -HSD type 2 im munoreactivity was detected in 27 of 36 (75%) endometrial hyperplasia and 1 7 of 46 (37%) carcinoma cases. 17 beta -HSD type 1 immunoreactivity was not detected in all the cases examined. In both endometrial hyperplasia and ca rcinoma cases there were significant positive correlations between 17 beta -HSD type 2 and progesterone receptor labeling index (LI). In carcinoma cas es, a significant inverse correlation was detected between 17 beta -HSD typ e 2 immunoreactiviy and age. In addition, 17 beta -HSD type 2 immunoreactiv ity was also correlated with 17 beta -HSD type 2 enzymatic activity, and se miquantitative analyses of 17 beta -HSD type 2 messenger RNA. No significan t correlations were detected between 17 beta -HSD type 2 and estrogen recep tor LI, Ki67 LI, amount of aromatase messenger RNA or histological grade.:T hese data indicated that the expression of 17 beta -HSD type 2 in hyperplas tic and/or neoplastic endometrium may represent altered cellular features t hrough hyperplastic and neoplastic transformation. However, 17 beta -HSD ty pe 2 may also play some protective and/or suppressive roles toward unoppose d estrogenic effects through inactivating E2 in situ, especially in premeno pausal patients.