Phospho-serine-118 estrogen receptor-α detection in human breast tumors in vivo

Purpose: To determine whether estrogen receptor (ER)-alpha specifically phosphorylated at Ser(118) is detectable in multiple human breast cancer biopsy samples. To gain insight into possible roles for P-Ser(118)-ERalpha in human breast cancer in vivo. Experimental Design: A specific antibody for P-Ser(118)-ERalpha was validated for immunohistochemistry (IHC), and Western blot analysis confirmed IHC results. IHC was used to determine the relationship of P-Ser(118)-ERalpha to known prognostic markers and active mitogen-activated protein kinase (MAPK; erk1/2) expression. Results: P-Ser(118)-ERalpha was significantly correlated with the expression of total ER, determined by ligand binding assay (r = 0.442, P = 0.002), but not with progesterone receptor expression or nodal status. P-Ser(118)-ERalpha was inversely correlated with histological grade (r = -0.34, P = 0.023), reflecting a similar trend for total ER (r = -0.287, P = 0.056). Categorical contingency analysis confirmed that P-Ser(118)-ERalpha was more frequently associated with lower than higher grade breast tumors (P = 0.038). In addition P-Ser(118)-ERalpha was significantly associated with detection of active MAPK (Erk1/2; Spearman r = 0.649, P < 0.0001; Fisher's exact test, P = 0.0004). Conclusions: P-Ser(118)-ERalpha detection is associated with a more differentiated phenotype and other markers of good prognosis in human breast cancer. P-Ser(118)-ERalpha is correlated with active MAPK in human breast tumor biopsies, suggesting the possibility that active MAPK either directly or indirectly has a role in the regulation of P-Ser(118)-ERalphat expression in vivo. These data provide evidence for a role of P-Ser(118)-ERalpha in human breast cancer in vivo.