High mRNA levels of 17 beta-hydroxysteroid dehydrogenase type 1 correlate with poor prognosis in endometrial cancer

Karlijn M. C. Cornel, Camilla Krakstad, Bert Delvoux, Sofia Xanthoulea, Balazs Jori, Marlies Y. Bongers, Gonda F. J. Konings, Loes F. S. Kooreman, Roy F. P. M. Kruitwagen, Helga B. Salvesen, Andrea Romano*, ENITEC

*Corresponding author for this work

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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 17 beta-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 (SULTIEI, that deactivates estrogens);

(c) the levels of aromatase (ARO), that converts androgen into estrogens.

mRNA levels of HSD17B1, HSD17B2, STS, SULTIEI 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 SULTIEI 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume442
Issue numberC
DOIs
Publication statusPublished - 15 Feb 2017

Keywords

  • Endometrial cancer
  • 17 beta-hydroxysteroid-dehydrogenase-type 1
  • 17 beta-hydroxysteroid-dehydrogenase-type 2
  • Steroid sulphatase
  • Estrogen-sulphotransferase
  • Aromatase
  • Estrogens
  • Prognosis
  • BREAST-CANCER
  • ESTROGEN
  • EXPRESSION
  • CARCINOMA
  • 17-BETA-ESTRADIOL
  • OVEREXPRESSION
  • BIOLOGY
  • ALPHA
  • CELLS
  • LINKS

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