Authors: M. Maher Hulou; M. Hulou, MD; Justin Fraser, MD (Lexington, KY)

Background: We aim to review the literature on chemical and immunohistochemical pituitary adenoma staining after resection to understand its role and potential predictive value. Methods: 365 articles related to pituitary adenoma and staining were reviewed. Information on histological studies, protocols and outcomes was extracted. Results: 16 papers were included, which encompassed 2,107 surgical specimens. Stains included TSH, FSH, LH, GH, prolactin, Ki-67, cyclin D1, and MGMT. One study found that 3% of pituitary adenomas stained positive for TSH, of which approximately 85% were nonfunctional. Most TSH-staining adenomas were plurihormonal, particularly costaining with GH. Two studies investigated the relationship between LH/FSH stains and pituitary tumors: Recurrence rates in LH positive group seem to be higher for non-functional pituitary adenomas (NFPAs) with large tumor volume and preoperative cavernous sinus invasion. Tumor recurrence rates were significantly higher for NPFAs that were positive for LH. Re-operation rate, but not recurrence rate, was higher in patients with positive FSH. Eight papers reported on KI-67 which seems to have a role in predicting invasion and acromegaly control with octreotide; however, the correlation between KI-67 and tumor size or recurrence is still controversial among the 8 studies. One study found that acromegalics with tumors that stain for prolactin and GH have a significantly higher aggressive clinical presentation. Expression of cyclin D1 in pituitary tumors was found to be related to cell proliferation, recurrence, and metastatic potential in one paper and nuclear cyclin D1 expression seems to be a good marker of aggressive behavior in pituitary tumors. Conclusion: There is a paucity of literature correlating pituitary adenoma pathological staining to outcomes. Furthermore, there is no uniformity with regard to staining protocols after resection. Published studies do suggest a role for hormonal stains, reflecting a need for further long-term and prospective evaluation.