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Amplification of HSD17B1 has prognostic significance in postmenopausal breast cancer

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Pathology/Cytology and Genetics, Division of Genetics, Linköping University Hospital, Linkoping, 581 85, Sweden

    Cecilia Gunnarsson

  2. Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, Linköping University, Linkoping, 581 85, Sweden

    Piiha-Lotta Jerevall, Karl Hammar, Birgit Olsson, Bo Nordenskjöld, Agneta Jansson & Olle Stål

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  1. Cecilia Gunnarsson
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  2. Piiha-Lotta Jerevall
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  3. Karl Hammar
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  4. Birgit Olsson
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  5. Bo Nordenskjöld
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  6. Agneta Jansson
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  7. Olle Stål
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Correspondence to Cecilia Gunnarsson.

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Gunnarsson, C., Jerevall, PL., Hammar, K. et al. Amplification of HSD17B1 has prognostic significance in postmenopausal breast cancer. Breast Cancer Res Treat 108, 35–41 (2008). https://doi.org/10.1007/s10549-007-9579-7

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  • DOI: https://doi.org/10.1007/s10549-007-9579-7

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