Verhoogde niveaus van twee onderdelen van het endocannabinoïde systeem (N-palmitoylethanolamine en N-arachidonoylethanolamine), weerspiegelen de productie van endometriumtumoren.
Door screening op verhoogde niveaus van deze stoffen kan het voor artsen gemakkelijker zijn om de mogelijke aanwezigheid van endometriumtumoren sneller te herkennen, wat leidt tot een mogelijk snellere diagnose en interventie. Verder onderzoek moet worden uitgevoerd om te zien of er een nog sterker verband bestaat tussen de dysregulatie van het endocannabinoïde systeem en endometriumkanker.
Objective: To identify new biochemical markers for endometrial cancer (EC). Recent evidence suggests that members of the endocannabinoid system (N-acylethanolamines) that bind to and activate receptors that are dysregulated in EC are involved in this tumour’s biology. These observations suggest increased N-acylethanolamine levels in the tissue that might appear in plasma and could be used as disease biomarkers.
Methods: N-arachidonoylethanolamine (anandamide, AEA) and the N-acylethanolaminesubstances, N-oleoylethanolamine (OEA), and N-palmitoylethanolamine (PEA) were quantiﬁed in plasma and endometrial tissue collected from 31 EC and seven atrophic controls using UHPLC-MS/MS. Receiver-operating characteristics (ROC) and logistic regression were used to determine diagnostic accuracy. Cannabinoid receptor 1 (CB1) and 2 (CB2) protein levels were determined by speciﬁc immunohistochemistry and histomorphometric analyses. Correlations between plasma and tissue levels of the three N-acylethanolamines and tissue levels of the three N-acylethanolamines and CB1 and CB2 receptor expression levels were determined using correlation analysis.
Results: Plasma and tissue AEA and PEA levels were signiﬁcantly (p < 0.05) higher in EC than controls whilst OEA levels were signiﬁcantly elevated in type 1 EC tissues but not in plasma. There were signiﬁcant positive correlations between plasma and tissue levels of AEA (R2 = 0.302, p = 0.008) and PEA (R2 = 0.182, p = 0.047), but not for OEA (R2 = 0.022, p =0.506). The diagnostic accuracies for EC were: sensitivity of 53.3%, speciﬁcity of 100% for plasma AEA (>1.36 nM); sensitivity of 73.3%, speciﬁcity of 100% for plasma PEA (>27.5 nM); and sensitivity of 93.3%, speciﬁcity of 28.6% for plasma OEA (>4.97 nM). Logistic regression increased the area under the ROC curve (AUC) from 0.781 for AEA, 0.857 for PEA, and 0.543 for OEA to a combined AUC of 0.933 for EC diagnosis. Signiﬁcant inverse correlations between tissue AEA (R2 =0.343, p = 0.003) and PEA (R2 = 0.384, p < 0.0001) levels and CB1 expression were observed.
No correlation between tissue levels of OEA and CB1 and tissue levels of any of the three N-acylethanolamines and CB2 protein expression were observed, except in the type 1 EC patients.
Conclusion: Since plasma AEA and PEA are signiﬁcantly elevated in patients with EC and a reﬂection of production by the endometrial tumour, then these lipids have the potential to be useful biomarkers for the early diagnosis of EC.