Steroid sulfatase (STS) hydrolyses biologically inactive
estrogen sulfates to active
estrogens, while
estrogen sulfotransferase (EST) sulfonates
estrogens to
estrogen sulfates. Information regarding the expression of STS in human
breast carcinoma tissues is still very limited compared to that of
aromatase or 17beta-hydroxysteroid
dehydrogenases (17beta-HSDs). In our study, EST and STS immunoreactivity was detected in
carcinoma cells in 50 and 84 out of 113
breast carcinomas (44.2% and 74.3%, respectively), which was also associated with
mRNA levels determined by RT/real-time PCR. Using microdissection/RT-PCR analyses, EST
mRNA was localized to both
carcinoma and intratumoral stromal cells, whereas STS was detected only in
carcinoma or parenchymal cells. STS immunoreactivity was positively associated with
tumor size. EST immunoreactivity was inversely correlated with
tumor size or lymph node status and was significantly associated with a decreased risk of recurrence and improved prognosis. These data suggest that both EST and STS play important roles in the regulation of in situ
estrogen production in human
breast cancer. In addition, EST is an independent prognostic factor in human
breast carcinoma and loss of EST may result in altered
estrogen metabolism in
hormone-dependent
breast cancer cells. An inhibition of intratumoral STS in the patients with
estrogen-dependent
breast carcinoma is also considered to provide more clinical benefits, especially to the patients in which primary source of an availability of intratumoral
estrogen is through STS rather than
aromatase.