Altered expression of lysophosphatidic acid receptors, in association with the synthesis of estrogens and androgens in type 1 endometrial cancer biology.

To establish association between two main lysophosphatidic acid (LPA) receptors (LPAR2 and LPAR1) with the synthesis of estrogens and androgens in type-1 endometrial carcinoma (EC), we evaluated correlation of LPARs expression with expression of steroid 5 alpha-reductase 2 - aromatase (SRD5A2), or cytochrome P450 family 19 subfamily A member 1-5α-reductase (CYP19A1) in EC. Moreover, we aimed to investigate SRD5A2 and CYP19A1 expression in type 1 endometrial cancer and normal endometrium with its correlation to selected clinicopathological features. The studied cancerous samples showed higher CYP19A1 and SRD5A2 expression comparing to normal endometria. We also documented positive correlations between LPAR1 and LPAR2 with responsible for proliferation SRD5A2 in EC tissue which suggests that intratumoral estrogen metabolism and synthesis are pivotal in endometrial carcinoma progression, with the involvement of LPA in this process. However, positive correlation between CYP19A1 and LPAR1 accounts for supporting role of LPA acting via LPAR1 in intratumoral DHT concentration and the ethiology of endometrial cancer progression. Also, owing to the highest expression of LPARs, CYP19A1 and SRD5A2 as well as their association with depth of myoinvasion and FIGO stage LPAR2 and LPAR1 seem to be the efficient candidate prognostic markers in the individual, targeted therapies for EC.