title: High mRNA levels of 17β-hydroxysteroid dehydrogenase type 1 correlate with poor prognosis in endometrial cancer.
abstract: Most endometrial cancers (ECs) are diagnosed at an early stage and have a good prognosis. However, 20-30% develop recurrence and have poor survival. Recurrence-risk prediction at diagnosis is hampered by the scarcity of prognostic markers. Most ECs are estrogen related, and recent studies show that estrogen exposure in EC is controlled intracrinally. We aim at assessing any association between patient prognosis and the pathways controlling the intracrine estrogen generation in EC: (a) the balance between 17β-hydroxysteroid-dehydrogenase-type 1 (HSD17B1), that generates active estrogens, and HSD17B2, converting active into poorly active compounds; (b) the balance between steroid sulphatase (STS, that activates estrogens) and estrogen-sulphotransferase (SULT1E1, that deactivates estrogens); (c) the levels of aromatase (ARO), that converts androgen into estrogens. mRNA levels of HSD17B1, HSD17B2, STS, SULT1E1 and ARO were determined among 175 ECs using cDNA microarray. Proteins were explored by immunohistochemistry. Patients with high mRNA of HSD17B1 had a poorer prognosis compared with those with low levels. Combining the expression of HSD17B1 and HSD17B2, patients with high tumour expression of HSD17B1 and low levels of HSD17B2 had the poorest prognosis. Contrarily, women that had high tumour levels of HSD17B2 and low of HSD17B1 had the best outcome. No differences were seen between mRNA level of other the genes analysed and prognosis. At the protein level, HSD17B2, STS and SULT1E1 were highly expressed, whereas HSD17B1 was low and ARO was almost absent. In conclusion, HSD17B1 is a promising marker to predict EC prognosis. Immunohistochemical detection of this protein in ECs has low sensitivity and should be improved for future clinical applications.
authors.affiliation: Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands; Department of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, The Netherlands.
authors.forename: Karlijn M C
authors.initials: KM
authors.lastname: Cornel
authors.affiliation: Centre for Cancer Biomarkers, Department of Biomedicine, University of Bergen, Norway; Department of Gynaecology and Obstetrics, Haukeland University Hospital, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Krakstad
authors.affiliation: Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: Delvoux
authors.affiliation: Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Sofia
authors.initials: S
authors.lastname: Xanthoulea
authors.affiliation: Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Balazs
authors.initials: B
authors.lastname: Jori
authors.affiliation: Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands; Department of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, The Netherlands.
authors.forename: Marlies Y
authors.initials: MY
authors.lastname: Bongers
authors.affiliation: Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Gonda F J
authors.initials: GF
authors.lastname: Konings
authors.affiliation: Department of Pathology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Loes F S
authors.initials: LF
authors.lastname: Kooreman
authors.affiliation: Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Roy Fpm
authors.initials: RF
authors.lastname: Kruitwagen
authors.affiliation: Department of Gynaecology and Obstetrics, Haukeland University Hospital, Norway; Centre for Cancer Biomarkers, Department of Biomedicine, University of Bergen, Norway.
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.affiliation: Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. Electronic address: a.romano@maastrichtuniversity.nl.
authors.forename: Andrea
authors.initials: A
authors.lastname: Romano
mesh_terms: D000368:Aged; D001141:Aromatase / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004960:Estradiol Dehydrogenases / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D043266:Steryl-Sulfatase / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens; D012333:RNA, Messenger; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; C523763:HSD17B2 protein, human; D001141:Aromatase; D015238:Sulfotransferases; C020122:estrone sulfotransferase; D043266:Steryl-Sulfatase
keywords: 17β-hydroxysteroid-dehydrogenase-type 1; 17β-hydroxysteroid-dehydrogenase-type 2; Aromatase; Endometrial cancer; Estrogen-sulphotransferase; Estrogens; Prognosis; Steroid sulphatase