Human 3 β-hydroxysteroid dehydrogenase type 1 in human breast cancer: clinical significance and prognostic associations.

Active sex steroids including estrogens and androgens are locally produced from circulating inactive steroids by various steroid-metabolizing enzymes, and play pivotal roles in the progression of hormone-dependent breast cancers. Human 3 β-hydroxysteroid dehydrogenase type 1 (3 β- HSD type 1) is a critical enzyme in the formation of all classes of active steroid hormones, and is also involved in the inactivation of potent androgen dihydrotestosterone ( DHT). Therefore, this enzyme is suggested to modulate active sex steroid production or inactivation, with a role in hormone-dependent breast cancer. The purpose of this study was to investigate the clinical significance of 3 β- HSD type 1 in human breast cancer. Using immunohistochemistry ( IHC), we evaluated 3 β- HSD type 1 expression in 161 human breast cancers and analyzed correlations of 3 β- HSD type 1 expression with various clinicopathological factors. Of 161 breast cancer cases, 3 β- HSD type 1 expression in cancer cells was detected in 119 cases (73.9%), and was positively correlated with estrogen receptor (ER)-positivity but not HER-2 status. In ER-positive cases ( n = 130), 3 β- HSD type 1 expression was inversely correlated with invasive tumor size ( P = 0.0009), presence of invasive region ( P = 0.0107), and lymphatic involvement ( P = 0.0004). 3 β- HSD type 1 expression was significantly associated with decreased risk of recurrence or improved prognosis by both univariate ( P = 0.0003 and P = 0.009, respectively) and multivariate ( P = 0.027 and P = 0.023, respectively) analyses. Our findings indicate that this enzyme is a prognostic factor in hormone-dependent breast cancer. [ABSTRACT FROM AUTHOR]