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

Abstract

ContextA sex difference in the progression of prolactin (PRL) tumors has been disputed for years.ObjectiveTo 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 methodsEighty-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 ERα expression was detected by immunohistochemistry and a score (0–12) calculated as the product of the percentage of positive nuclei and the staining intensity.ResultsWe 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 ERα expression was 1 in men (range, 0–8) and 8 in women (range, 0–12) (P<0.0001). The expression of ERα 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 ERα expression.ConclusionsPRL tumors in men are characterized by lower ERα expression, which is related to higher tumor grades, resistance to treatment, and an overall worse prognosis.