Human 3β‐hydroxysteroid dehydrogenase type 1 in human breast cancer: clinical significance and prognostic associations. (3rd May 2016)

• Record Type: Journal Article
• Authors: Hanamura, Toru; Ito, Tokiko; Kanai, Toshiharu; Maeno, Kazuma; Shimojo, Yasuyo; Uehara, Takeshi; Suzuki, Takashi; Hayashi, Shin‐ichi; Ito, Ken‐ichi
• Is Part Of: Cancer medicine. Volume 5:Number 7(2016:Jul.)
• Page Start: 1405
• Page End: 1415
• Publication Date: 2016-05-03
• Subjects: 3β‐hydroxysteroid dehydrogenase type 1 -- breast cancer -- clinical significance -- prognosis -- steroid metabolism; 616.994005
• DOI: 10.1002/cam4.708
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: 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 : In this study, we applied immunohistochemistry (IHC) to investigate the clinical and prognostic significance of 3β‐HSD type 1, which may regulate in situ production or inactivation of active sex steroids in hormone‐dependent breast cancers. This is the first study to indicate that 3β‐HSD type 1 is potent prognostic factor in hormone‐dependent breast cancer.