Amplification of HSD17B1 has prognostic significance in postmenopausal breast cancer
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In situ synthesis of estrogens is believed to be of great importance for the progression of breast cancer. In postmenopausal women most estrogens are synthesized in peripheral hormone-target tissues from circulating precursor steroids, by the enzymes involved in formation of active estrogens. One of the enzymes involved in this process is 17β-hydroxysteroid dehydrogenase (17β-HSD) type 1. This enzyme catalyzes the interconversion of estrone (E1) to the biologically more potent estradiol (E2). The gene coding for 17β-HSD type 1 (HSD17B1) is located at 17q12-21. The aim of this study was to investigate altered gene copy number of HSD17B1 in breast cancer. We used real-time PCR and examined 387 postmenopausal breast tumors for amplification of HSD17B1, and if an increased mRNA level of this enzyme is associated with amplification of the gene. We also investigated whether amplification of HSD17B1 has a prognostic value. There was a significant correlation between gene copy number of HSD17B1 and mRNA expression level (P = 0.00002). ER-positive patients with amplification of HSD17B1 showed lower breast cancer survival than patients without amplification (P = 0.025). Among ER-negative patients there was no significant correlation between increased gene copy number of HSD17B1 and prognosis. Furthermore, we found that amplification of the gene had prognostic significance in multivariate analysis adjusting for other clinicopathological variables.
Keywords17q 17β-HSD Breast cancer Estrogen HSD17B1 Real-time PCR
This work was funded by the Swedish Cancer Society and Östergötland County Council research and development fund. There is no conflict of interest that would prejudice impartiality.
- 17.Stål O, Borg Å, Fernö M, Källström A-C, Malmström P, Nordenskjöld B, members of the South Sweden Breast Cancer Group, the Southeast Sweden Breast Cancer Group (2000) ErbB2 status and the benefit from two or five years of adjuvant tamoxifen in postmenopausal early stage breast cancer. Ann Oncol 11:1545–1550PubMedCrossRefGoogle Scholar
- 23.Jansson A, Gunnarsson C, Stål O (2006) Proliferative responses to altered 17beta-hydroxysteroid dehydrogenase (17HSD) type 2 expression in human breast cancer cells are dependent on endogenous expression of 17HSD type 1 and the oestradiol receptors. Endocr Relat Cancer 13:875–884PubMedCrossRefGoogle Scholar
- 24.Speirs V, Green AR, Atkin SL (1998) Activity and gene expression of 17beta-hydroxysteroid dehydrogenase type I in primary cultures of epithelial and stromal cells derived from normal and tumourous human breast tissue: the role of IL-8. J Steroid Biochem Mol Biol 67:267–274PubMedCrossRefGoogle Scholar
- 27.Gunnarsson C, Jansson A, Holmlund B, Ferraud L, Nordenskjöld B, Rutqvist LE, Skoog L, Stål O (2006) Expression of COX-2 and steroid converting enzymes in breast cancer. Oncol Rep 16:19–24Google Scholar