Chan KKL et al. -The histotype-specific expression pattern of estrogen receptors (ERs) suggests that personalized treatment for women based on ER expression using selective estrogen receptor modulators may improve response rate. In addition nuclear ER-beta5 is a potential prognostic marker and therapeutic target in ovarian cancer.

Methods
ER-alpha, ER-beta1, ER-beta2, and ER-beta5 expression were evaluated by immunohistochemistry in 106 ovarian cancer tissues.
The association between ER expression and clinicopathologic parameters or prognosis was analyzed.
Ectopic expression of ER-beta2 and ER-beta5 followed by functional assays were performed in ovarian cancer cell lines to detect effects on cell invasion and proliferation.

Results
Asignificantly higher nuclear ER-alpha and nuclear ER-beta5 and lower cytoplasmic ER-alpha expression was demonstrated in advanced cancers. Significantly lower ER-beta1 expression was also detected in high-grade cancers.
Significant loss of nuclear ER-alpha and cytoplasmic ER-beta2 expression was observed in clear cell histologic subtypes.
Higher nuclear ER-beta5 and lower cytoplasmic ER-beta5 expression was associated with serous/clear cell subtypes, poor disease-free, and overall survival.
Positive cytoplasmic ER-alpha and higher cytoplasmic ER-beta1 expression were significantly associated with better disease-free and overall survival. Nuclear ER-beta5 is an independent prognostic factor for overall survival. Overexpression of ER-beta5 enhanced ovarian cancer cell migration, invasion, and proliferation via FAK/c-Src activation, whereas ER-beta2 induced cell migration and invasion.