FSH Levels Are Related to E-cadherin Expression and Subcellular Location in Nonfunctioning Pituitary Tumors

• Published in: The journal of clinical endocrinology and metabolism 2020-08, Vol.105 (8), p.2587-2594
• Main Authors: Kolnes, Anders J, Øystese, Kristin A B, Olarescu, Nicoleta C, Ringstad, Geir, Berg-Johnsen, Jon, Casar-Borota, Olivera, Bollerslev, Jens, Jørgensen, Anders P
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Antigens, CD - analysis; Antigens, CD - metabolism; Brain cancer; Brain tumors; Cadherins - analysis; Cadherins - metabolism; Cell Membrane - metabolism; Cell Nucleus - metabolism; Clinical s; Development and progression; E-cadherin; Epithelial cells; Epithelial-Mesenchymal Transition; Estrogen; Estrogen Receptor alpha - metabolism; Estrogen receptors; Female; Follicle Stimulating Hormone - analysis; Follicle Stimulating Hormone - metabolism; Follicle-stimulating hormone; FSH; Glycoproteins; Gonadotrophs - cytology; Gonadotrophs - metabolism; Humans; Immunohistochemistry; Invasiveness; Luteinizing hormone; Male; Mesenchyme; Middle Aged; mRNA; Neuroendocrine tumors; Pathology; Patologi; Phenotypes; PitNET; Pituitary; Pituitary (anterior); pituitary adenoma; Pituitary gland; Pituitary gland tumors; Pituitary Neoplasms - blood; Pituitary Neoplasms - pathology; Polymerase chain reaction; Retrospective Studies; Stem cells; Tumors
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa281

Abstract Context Gonadotroph pituitary neuroendocrine tumors (PitNETs) can express follicle-stimulating hormone (FSH) and luteinizing hormone (LH) or be hormone negative, but they rarely secrete hormones. During tumor development, epithelial cells develop a mesenchymal phenotype. This process is characterized by decreased membranous E-cadherin and translocation of E-cadherin to the nucleus. Estrogen receptors (ERs) regulate both E-cadherin and FSH expression and secretion. Whether the hormone status of patients with gonadotroph PitNETs is regulated by epithelial-to-mesenchymal transition (EMT) and ERs is unknown. Objectives To study the effect of EMT on hormone expression in gonadotroph nonfunctioning (NF)-PitNETs. Design Molecular and clinical analyses of 105 gonadotroph PitNETs. Immunohistochemical studies and real-time quantitative polymerase chain reaction were performed for FSH, LH, E-cadherin, and ERα. Further analyses included blood samples, clinical data, and radiological images. Setting All patients were operated on in the same tertiary referral center. Results NF-PitNET with high FSH expression had decreased immunohistochemical staining for membranous E-cadherin (P < .0001) and increased staining for nuclear E-cadherin (P < .0001). Furthermore, high FSH expression was associated with increased ERα staining (P = .0002) and ERα mRNA (P = .0039). Circulating levels of plasma-FSH (P-FSH) correlated with FSH staining in gonadotroph NF-PitNET (P = .0025). Tumor size and invasiveness was not related to FSH staining, E-cadherin, or ERα. LH expression was not associated with E-cadherin or ERα. Conclusion In gonadotroph PitNETs, FSH staining is related to E-cadherin, ERα expression, and circulating levels of P-FSH. There was no association between FSH staining and invasiveness. The clinical significance of these findings will be investigated in ongoing prospective studies.