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.