Expression of estrogen receptor-related receptor isoforms and clinical significance in endometrial adenocarcinoma

Estrogen receptor-related receptors (ERRs) are members of orphan nuclear receptors closely related to the estrogen receptors (ERs). Researches showed that the ERRs bound to estrogen response elements and interfered in the ER signal pathway. Therefore, it might be associated with estrogen-dependent diseases. The purpose of this study was to explore whether ERRs were involved in the tumorigenesis of endometrial adenocarcinoma. We examined the expression of ERRs in endometrial adenocarcinoma and normal endometrium using semiquantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Clinicopathologic features including FIGO stage, histologic grade, myometrial invasion, and nodal metastasis were reviewed. Results showed that messenger RNA (mRNA) levels of ERR alpha, ERR beta, and ERR gamma were positively associated with the immunoreactivities (P = 0.009, P = 0.014, and P = 0.001, respectively). The expression rate and relative level of ERR alpha mRNA in ER alpha-positive endometrial adenocarcinomas were lower than in normal endometriums (P = 0.049 and P = 0.023), whereas the relative level of ERR gamma mRNA in ER alpha-positive endometrial adenocarcinomas was higher than in normal endometriums (P = 0.014). Expression of ERR alpha mRNA was positively correlated with FIGO stage (P = 0.019) and myometrial invasion (P = 0.043). A negative correlation was observed between expression of ERR gamma mRNA and nodal metastasis (P = 0.021). Results suggested that ERR alpha and ERR gamma might participate in the tumorigenesis of endometrial adenocarcinoma. ERR alpha and ERR gamma are promising to be new prognostic factors in endometrial adenocarcinoma.