Abnormal expression of 17β-hydroxysteroid dehydrogenases in breast cancer predicts late recurrence
2001 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 61, no 23, 8448-8451 p.Article in journal (Refereed) Published
The 17β-hydroxysteroid dehydrogenase (17β-HSD) enzymes are involved in the interconversion of biologically active and inactive sex steroids and are considered to play a critical role in the in situ metabolism of estrogen, especially in estrogen-dependent breast cancer. The gene encoding 17β-HSD type 2 is located at 16q24.1-2, and earlier studies have shown that allelic loss in this region is an early and frequent event in breast cancer progression. Recurrence of hormone-dependent breast cancer frequently occurs several years after the primary treatment. The aim of this study was to investigate whether the expression of 17β-HSD types 1 and 2 differs in tumors from patients with late relapses (>5 years) compared with controls without recurrence after long-term follow-up. Using real-time reverse transcription-PCR, we found that the normal mammary gland expressed both 17β-HSD types 1 and 2, whereas the tumors frequently lacked detectable levels of type 2. Only 10% of the estrogen receptor-positive tumors expressed type 2, whereas 31% of the ERnegative tumors did so (P = 0.031). In a case-control series of 84 patients, a high level of 17β-HSD type 1 indicated increased risk to develop late relapse of breast cancer (odds ratio, 3.0; 95% confidence interval, 1.0–12.6; P = 0.041), whereas retained expression of type 2 indicated decreased risk (odds ratio, 0.25; 95% confidence interval, 0.05–1.2; P = 0.050). In multivariate analysis of the estrogen receptor-positive patients, the absence of 17β-HSD type 2 combined with a high expression of type 1 showed prognostic significance (P = 0.016) in addition to DNA aneuploidy (P = 0.0058), whereas progesterone receptor status did not (P = 0.71). These findings suggest that abnormal expression of 17β-HSD isoforms has prognostic significance in breast cancer and that altered expression of these enzymes may have importance in breast cancer progression.
Place, publisher, year, edition, pages
2001. Vol. 61, no 23, 8448-8451 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-24885PubMedID: 11731426Local ID: 9287OAI: oai:DiVA.org:liu-24885DiVA: diva2:245208