Immunohistochemical Detection of Estrogen Receptor Alpha in Pituitary Adenomas and Its Correlation with Cellular Replication

With the aim of evaluating the relationship between pituitary tumorigenesis and the presence of estrogen receptor-α (ERα) by immunohistochemistry (IH) and their relevance to patients’ clinical presentation, hormonal phenotypes of adenomas, preoperative neuroimaging findings, and the index of cellular replication MIB-1, a study was conducted with material from 91 women and 67 men with pituitary adenomas. The patients had acromegaly (29.7%), Cushing’s disease (14.6%), hyperprolactinemic syndrome (20.9%), and clinically nonfunctioning tumors (34.8%). Of the patients, 14.6% had microadenomas, 52.5% had macroadenomas with or without suprasellar growth, 28.5% had invasive macroadenomas and in 4.4% the adenoma was not visualized. IH showed that 43 were positive for growth hormone (GH), 16 for corticotropin (ACTH), 18 for prolactin (PRL), 18 for PRL+GH, 6 for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), 15 had a plurihormonal reaction, and 42 had nonfunctioning adenomas. The presence of ERα was positive in 9/158 adenomas with a median value for the percentage of labeled cells of 42.89%, and in 6/16 controls (autopsy samples) with a median value for the percentage of labeled cells of 0.024%. ERα was significantly more prevalent in controls than in patients with adenomas (37.5 versus5.7%; p = 0.001); however, the mean ERα concentration in adenomas was significantly greater than in controls (42.89 versus 0.024%; p < 0.001). No significant difference in the concentration of ERα was found across the clinical presentations, hormonal phenotypes or findings of preoperative CT. Among the ERα-positive adenomas, ERα values were significantly greater in invasive macroadenomas (80%) than in microadenomas (3.33%). MIB-1 values did not differ significantly between ERα-positive and -negative adenomas, nor did the correlation between ERα values and the MIB-1 index attain significance in the total sample, even when only ERα-positive adenomas and positive MIB-1 indexes were considered. It was concluded that, when present in pituitary tumors, ERα exhibits a high concentration, and is more common in nonfunctioning and invasive adenomas, but absent in ACTH-secreting ones.