Fsh Levels Are Related To E-Cadherin Expression And Subcellular Location In Nonfunctioning Pituitary Tumors

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 ER alpha. 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 ER alpha staining (P = .0002) and ER alpha 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 ER alpha. LH expression was not associated with E-cadherin or ER alpha.Conclusion: In gonadotroph PitNETs, FSH staining is related to E-cadherin, ER alpha 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.