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- Title
FSH Levels Are Related to E-cadherin Expression and Subcellular Location in Nonfunctioning Pituitary Tumors.
- Authors
Kolnes, Anders J.; Øystese, Kristin A. B.; Olarescu, Nicoleta C.; Ringstad, Geir; Berg-Johnsen, Jon; Casar-Borota, Olivera; Bollerslev, Jens; Jørgensen, Anders P.
- Abstract
<bold>Context: </bold>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.<bold>Objectives: </bold>To study the effect of EMT on hormone expression in gonadotroph nonfunctioning (NF)-PitNETs.<bold>Design: </bold>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.<bold>Setting: </bold>All patients were operated on in the same tertiary referral center.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
PITUITARY tumors; PROLACTIN; GONADOTROPIN; CELL adhesion molecules; REVERSE transcriptase polymerase chain reaction; EPITHELIAL-mesenchymal transition; ANTIGEN analysis; GLYCOPROTEIN analysis; PROTEIN metabolism; PITUITARY gland; FOLLICLE-stimulating hormone; CELL membranes; RETROSPECTIVE studies; CELL nuclei; GLYCOPROTEINS; ANTIGENS
- Publication
Journal of Clinical Endocrinology & Metabolism, 2020, Vol 105, Issue 8, p1
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgaa281