17 beta-hydroxysteroid dehydrogenase type 1 and type 2 in ductal carcinomain situ and intraductal proliferative lesions of the human breast

17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs) are involved in the in terconversion of biologically active and inactive sex steroids and are cons idered to play important roles in the in situ metabolism of estrogen in var ious estrogen dependent tissues. 17 beta-HSD type 1 catalyzes primarily the reduction of estrone (E1) to estradiol (E2) whereas 17 beta -HSD type 2 ca talyzes primarily the oxidation of E2 to E1. However, the possible biologic al roles of these estrogen metabolizing isozymes in human breast cancer, es pecially in carcinogenesis of the human breast, have not been examined in d etail. Because of the potential roles of estrogens in the early stages of h uman breast carcinogenesis, we have examined the immunolocalization of 17 b eta -HSD type 1 and type 2 isozymes and estrogen receptor alpha(ER alpha) i n both normal human breast tissue and in breast cancers, including ductal c arcinoma in situ (DCIS), proliferative disease without atypia (PDWA) or fib rocystic disease and atypical ductal hyperplasia (ADH). We also correlated these findings with clinicopathological findings, Ki67 antigen, progesteron e receptor (PR), c-erbB-2, and p53. 17 beta-HSD type 2 immunoreactivity was sporadically detected in non- proliferative or Ki67 negative ductal epithe lia of normal breast, but rarely in breast carcinoma cells. 17 beta -HSD ty pe 1 immunoreactivity was detected in 12/22 (54.5%) PDWA cases, 8/26 (30.8% ) ADH cases, and 25/40 (62.5%) DCIS cases, respectively. 17 beta -HSD type 1 immunoreactivity was not statistically correlated with the age of the pat ients, Ki67 labeling index (LI), and PR LI, p-53 and c-erbB-2 immunoreactiv ity. There was no significant correlation between ER alpha LI and 17 beta - HSD type 1 immunoreactivity. There was a positive correlation between ER a lpha and Ki67 LI in PDWA, whereas a negative correlation was detected betwe en ER alpha and Ki67 LI in DCIS. There was no correlation between ER alpha and Ki67 LI in ADH. These results suggest that in human breast epithelial c ells, development of ADH and DCIS may be associated with the loss and/or de viation of oestrogen dependent regulation of cell proliferation.