Amplification of HSD17B1 and ERBB2 in primary breast cancer.
Estrogens play a crucial role in the development of breast cancer. Estradiol can be produced in the breast tissue in situ, and one of the enzymes involved in this process is 17beta-hydroxysteriod dehydrogenase (17beta-HSD) type 1 that catalyzes the interconversion of estrone (E1) to the biologically more potent estradiol (E2). The gene coding for 17beta-HSD type 1 (HSD17B1) is located at 17q12-21, close to the more studied ERBB2 and BRCA1. The aim of this study was to investigate if HSD17B1 shows an altered gene copy number in breast cancer. We used real-time PCR and examined 221 postmenopausal breast tumors for amplification of HSD17B1 and ERBB2. In all, 32 tumors (14.5%) showed amplification of HSD17B1 and 21% were amplified for ERBB2. Amplification of the two genes was correlated (P=0.00078) and in 14 tumors (44%) with amplification of HSD17B1, ERBB2 was co amplified. The patients with amplification in at least one of the genes had a significantly worse outcome than patients without (P=0.0059). For estrogen receptor (ER)-positive patients who received adjuvant tamoxifen, amplification of HSD17B1 was related to decreased breast cancer survival (P=0.017), whereas amplification of ERRB2 was not. Amplification of HSD17B1 might be an indicator of adverse prognosis among ER-positive patients, and possibly a mechanism for decreased benefit from tamoxifen treatment.
Gunnarsson
Cecilia
C
Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Sweden.
Ahnström
Marie
M
Kirschner
Kristina
K
Olsson
Birgit
B
Nordenskjöld
Bo
B
Rutqvist
Lars Erik
LE
Skoog
Lambert
L
Stål
Olle
O
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D006801:Humans; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
D015067:17-Hydroxysteroid Dehydrogenases; D017931:DNA Primers; D018719:Erb-b2 Receptor Tyrosine Kinases