Estrogen Receptor α, a Sex-Dependent Predictor of Aggressiveness in Nonfunctioning Pituitary Adenomas: SSTR and Sex Hormone Receptor Distribution in NFPA

Context: Nonfunctioning pituitary adenomas (NFPAs) are fairly common and require a multidisciplinary approach. Reliable markers of a clinically aggressive course are lacking. Medical treatment is not available, and transsphenoidal surgery is the preferred primary treatment. Objective: We aimed to characterize the somatostatin, estrogen, and progesterone receptor distribution for NFPAs and compare it with factors of tumor aggressiveness. Design: Tumor samples for immunohistochemistry (n = 145) and quantitative reverse transcription polymerase chain reaction (n = 106) analyses of somatostatin receptor (SSTR) 1, SSTR2, SSTR3, SSTR5, estrogen receptor alpha (ER alpha), and progesterone receptor (PR) were measured by immunoreactive score (IRS) andmessenger RNA relative quantity and retrospectively compared with variables of aggressiveness. Setting: All patients were operated at the same tertiary referral center. Participants: A total of 164 patients with NFPA and tumor tissue from the primary operation were included. Results: SSTR3 was expressed abundantly by immunohistochemistry in all NFPAs. The IRS of ER alpha correlated with that of SSTR2 in male patients only (males, P<0.001; females, P = 0.8). Low ER alpha level was linked to a higher reintervention rate (P = 0.001) and earlier reintervention (P = 0.004) in male patients only (females, P = 0.95 and P = 0.65, respectively). Absence of ER alpha together with age provided a good prediction model for reintervention in male patients with gonadotroph adenomas. Conclusions: SSTR3 is expressed abundantly in NFPAs and is therefore a possible target for medical treatment. Absence of ER alpha together with young age may predict tumor recurrence in groups of NFPAs. Further validation in systematic prospective studies is needed.