Amplification of HSD17B1 has prognostic significance in postmenopausal breast cancer.
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 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1. This enzyme 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. 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.
Gunnarsson
Cecilia
C
Department of Pathology/Cytology and Genetics, Division of Genetics, Linköping University Hospital, Linkoping, Sweden. cecilia.gunnarsson@lio.se
Jerevall
Piiha-Lotta
PL
Hammar
Karl
K
Olsson
Birgit
B
Nordenskjöld
Bo
B
Jansson
Agneta
A
Stål
Olle
O
D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D017698:Postmenopause; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human