Relation between outcomes and expression of estrogen receptor‐α phosphorylated at Ser167 in endometrioid endometrial cancer

Both ligand‐dependent and ligand‐independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation and results in activation of the ERα‐dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is also known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and MAPK/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated‐ERα at Ser¹⁶⁷ (p‐Ser¹⁶⁷‐ERα). However, the expression of p‐Ser¹⁶⁷‐ERα in EEC and its prognostic role in ECC is largely unexplored. The purpose of the present study was to investigate the expression of p‐Ser¹⁶⁷‐ERα in ECC and its relationship with prognosis. Immunohistochemical staining of primary EEC surgical specimens (n = 103) was carried out using antibodies specific for p‐Ser¹⁶⁷‐ERα and for p‐mTOR/p‐S6K1 and p‐MAPK/p‐RSK. The correlation of p‐Ser¹⁶⁷‐ERα expression with clinicopathological features and survival of ECC was studied. Patients that were positive for nuclear p‐Ser¹⁶⁷‐ERα had significantly shorter relapse‐free survival, and although the result was not significant, levels of nuclear p‐Ser¹⁶⁷‐ERα tended to be higher in advanced‐stage ECC patients. Nuclear p‐Ser¹⁶⁷‐ERα was significantly positively correlated with p‐MAPK and p‐S6K1, and with significantly shorter relapse‐free survival in EEC.