Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth

Abstract

Context: A sex difference in the progression of prolactin (PRL) tumors has been disputed for years. Objective: To compare tumor characteristics and postoperative clinical course between men and women, and correlate data with estrogen receptor alpha (ERα (ESR1)) expression status. Design, patients, and methods: Eighty-nine patients (59 women and 30 men) operated on for a prolactinoma and followed for at least 5 years were selected. Tumors were classified into five grades according to their size, invasion, and proliferation characteristics. The ERa expression was detected by immunohistochemistry and a score (0-12) calculated as the product of the percentage of positive nuclei and the staining intensity. Results:We found a significant preponderance of high-grade tumors among men and a lower surgical cure rate in men (23%) than in women (71%). Patients resistant to medical treatment were mainly men (7/8), six of whom showed tumor progression despite postoperative medical treatment, which led to multiple therapies and eventually death in three. The median score for ERa expression was 1 in men (range, 0-8) and 8 in women (range, 0-12) (P<0.0001). The expression of ERa was inversely correlated with tumor size (r=-0.59; P<0.0001) and proliferative activity. All dopamine agonist-resistant tumors and all grade 2b (invasive and proliferative) tumors (from ten men and four women) were characterized by low ERa expression. Conclusions: PRL tumors in men are characterized by lower ERa expression, which is related to higher tumor grades, resistance to treatment, and an overall worse prognosis.