RESUMO
Endometrial cancer is one of the most common female pelvic cancers and has been considered an androgen-related malignancy. Several studies have demonstrated the anti-cell proliferative effect of androgen on endometrial cancer cells; however, the mechanisms of the anti-cancer effect of androgen remain largely unclear. 17ß-hydroxysteroid dehydrogenase type 2 (17ß-HSD2), which catalyzes the conversion of E2 to E1, is known to be upregulated by androgen treatment in breast cancer cells. In this study, we therefore focused on the role of androgen on estrogen dependence in endometrial cancer. Dihydrotestosterone (DHT) was found to induce 17ß-HSD2 mRNA and protein expression in HEC-1B endometrial cancer cells. DHT could also inhibit cell proliferation of HEC-1B when induced by estradiol treatment. In 19 endometrioid endometrial adenocarcinoma (EEA) tissues, intratumoral DHT concentration was measured by liquid chromatography/electrospray tandem mass spectrometry and was found to be significantly correlated with 17ß-HSD2 immunohistochemical status. We further examined the correlations between 17ß-HSD2 immunoreactivity and clinicopathological parameters in 53 EEA tissues. 17ß-HSD2 status was inversely associated with the histological grade, clinical stage, and cell proliferation marker Ki-67, and positively correlated with progesterone receptor expression. 17ß-HSD2 status tended to be positively associated with androgen receptor status. In 53 EEA cases, the 17ß-HSD2-positive group tended to have better prognosis than that for the negative group with respect to progression-free survival and endometrial cancer-specific survival. These findings suggest that androgen suppresses the estrogen dependence of endometrial cancer through the induction of 17ß-HSD2 in endometrial cancer.
Assuntos
Androgênios/farmacologia , Carcinoma Endometrioide/metabolismo , Di-Hidrotestosterona/farmacologia , Neoplasias do Endométrio/metabolismo , Estradiol Desidrogenases/metabolismo , Transdução de Sinais , Idoso , Androgênios/metabolismo , Carcinoma Endometrioide/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Di-Hidrotestosterona/metabolismo , Neoplasias do Endométrio/patologia , Estradiol Desidrogenases/genética , Feminino , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Endometrial carcinoma, especially endometrioid endometrial adenocarcinoma, is an estrogen-dependent tumor that is similar to breast cancer. Androgen is closely associated with other steroid hormones, but its correlation with endometrioid endometrial adenocarcinoma remains largely unclear. We previously demonstrated the expression of the androgen receptor, 5α-reductase type 1, and 5α-reductase type 2 in endometrioid endometrial adenocarcinoma tissue, but androgen action and its correlation with prognosis are unknown. In this study, we measured the tissue and serum concentrations of androgen and performed immunohistochemical analyses of androgen-associated factors in 41 patients. In 86 additional patients, we performed the same immunohistochemical analyses to identify correlations associated with prognosis. We found that 5α-reductase type 1 was associated with intratumoral dihydrotestosterone concentrations, and it was an independent prognostic factor in endometrioid endometrial adenocarcinoma. The poor prognosis of patients negative for both androgen receptor and 5α-reductase type 1 suggests that androgens have inhibitory effects on tumor growth.
