title: 17beta-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer.
abstract: The 17beta-hydroxysteroid dehydrogenase (17HSD) enzymes are involved in the local regulation of sex steroids. The 17HSD type 1 enzyme catalyses the interconversion of the weak oestrone (E1) to the more potent oestradiol (E2), whereas 17HSD type 2 catalyses the oxidation of E2 to E1. The aim of this study was to correlate the expression of these enzymes in the tumour with the recurrence-free survival of tamoxifen-treated breast cancer patients. We used real-time reverse transcriptase PCR to investigate the mRNA expression of 17HSD types 1 and 2 in tumour samples from 230 postmenopausal patients. For the patients with oestrogen receptor (ER)-positive breast cancer, we found a statistically significant positive correlation between recurrence-free survival and expression of 17HSD type 2 (P=0.026). We examined the ratio of 17HSD types 2 and 1, and ER-positive patients with low ratios showed a significantly higher rate of recurrence than those with higher ratios (P=0.0047). ER positive patients with high expression levels of 17HSD type 1 had a significantly higher risk for late relapse (P=0.0051). The expression of 17HSD types 1 and 2 in breast cancer differs from the expression of these enzymes in normal mammary gland, and this study indicates that the expression has prognostic significance in breast cancer.
authors.affiliation: Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, Linköping, Sweden. cecilia.gunnarsson@lio.se
authors.forename: C
authors.initials: C
authors.lastname: Gunnarsson
authors.forename: E
authors.initials: E
authors.lastname: Hellqvist
authors.forename: O
authors.initials: O
authors.lastname: Stål
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D018572:Disease-Free Survival; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000178:diet therapy / Q000201:enzymology; D011379:Prognosis; D013629:Tamoxifen / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D004967:Estrogens; D013629:Tamoxifen; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase