Cannabinoid receptor expression in estrogen-dependent and estrogen-independent endometrial cancer

The lack of good diagnostic/prognostic biomarkers and the often late presentation of endometrial cancer (EC) hinders the amelioration of the morbidity and mortality rates associated with this primarily estrogen-driven disease, a disease that is becoming more prevalent in the population. Previous studies on the expression of the classical cannabinoid receptors, CB1 and CB2, suggest these could provide good diagnostic/prognostic biomarkers for EC but those observations have been contradictory. In this study, we sought to resolve the inconsistency of CB1 and CB2 expression levels in different EC studies. To that end, we used qRT-PCR and immunohistochemistry (IHC) for CB1 and CB2 in endometrial biopsies from women with or without EC and found that transcript levels for both CB1 and CB2 were significantly decreased by 90 and 80%, respectively in EC. These observations were supported by histomorphometric studies where CB1 and CB2 staining intensity was decreased in all types of EC. These data suggest that the loss of both types of CB receptors is potentially involved in the development of or progression of EC and that CB1 and CB2 receptor expression could serve as useful histological markers and therapeutic targets in the treatment of or prevention of EC.