title: Human 3β-hydroxysteroid dehydrogenase type 1 in human breast cancer: clinical significance and prognostic associations.
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 3β-hydroxysteroid dehydrogenase type 1 (3β-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 3β-HSD type 1 in human breast cancer. Using immunohistochemistry (IHC), we evaluated 3β-HSD type 1 expression in 161 human breast cancers and analyzed correlations of 3β-HSD type 1 expression with various clinicopathological factors. Of 161 breast cancer cases, 3β-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), 3β-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). 3β-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.
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hanamura
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan.
authors.forename: Tokiko
authors.initials: T
authors.lastname: Ito
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Kanai
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Maeno
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Nagano, Japan.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Shimojo
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Nagano, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uehara
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Center for Regulatory Epigenome and Diseases, Department of Molecular and Functional Dynamics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Ito
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D015096:3-Hydroxysteroid Dehydrogenases
keywords: 3β-hydroxysteroid dehydrogenase type 1; breast cancer; clinical significance; prognosis; steroid metabolism