Abstract
BACKGROUND: In ovarian cancer, the role of estrogen receptors (ERs), particularly of ERβ, being suggested as tumor suppressor in breast and prostate cancer, remains unclear. We examined the expression of nuclear and cytoplasmic ERβ in ovarian cancer and correlated it with expression of ovarian cancer markers CA125, CEA and CA72-4, steroid hormone receptors ERα and PR, cancer-associated genes EGFR, p53, HER2 and proliferation marker Ki-67. Additionally we examined to what extent expression of ERβ and the other proteins affects survival of ovarian cancer patients. METHODS: We established a tissue microarray from 171 ovarian cancer patients and performed immunohistochemical analyses of the mentioned proteins. RESULTS: Nuclear ERβ was detected in 47.31% of the ovarian cancer tissues and cytoplasmic expression of this receptor was observed in 23.08%. Nuclear expression of ERβ was significantly decreased in the G3 subgroup compared to better differentiated cancers (p < 0.01) and correlated with ovarian cancer markers CEA (95% CI 0.1598-0.4465; p < 0.0001) and CA72-4 (95% CI 0.05953-0.3616; p < 0.01). Cytoplasmic ERβ expression correlated with EGFR levels (95% CI 0.1059-0.4049; p < 0.001). ERα expression was associated with expression of CA125 and PR. Overall survival of patients with tumors expressing cytoplasmic ERβ was significant longer compared to those with ERβ-negative ovarian cancer (chi-square statistic of the log-rank, p < 0.05). Progression-free survival was dependent on expression of PR (chi-square statistic of the log-rank, p < 0.05) and Ki-67 (p = 0.05). CONCLUSIONS: Our data suggest an important, but distinct role of nuclear and cytoplasmic ERβ expression in ovarian cancer and encourage further studies on its role in this cancer entity.