FSH levels are related to E-cadherin expression and subcellular location in non-functioning pituitary tumors.

CONTEXT: Gonadotroph pituitary neuroendocrine tumors (PitNETs) can express FSH and 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 (ER) regulate both E-cadherin and FSH expression and secretion. Whether the hormone status of patients with gonadotroph PitNETs is regulated by EMT and estrogen receptors is unknown. OBJECTIVES: To study the effect of epithelial-to-mesenchymal transition (EMT) on hormone expression in gonadotroph non-functioning pituitary neuroendocrine tumors (NF-PitNETs). DESIGN: Molecular and clinical analyses of 105 gonadotroph PitNETs. Immunohistochemical studies and real-time-qPCR were performed for FSH, LH, E-cadherin and ERα. Further analyses included blood samples, clinical data and radiological images. SETTING: All patients were operated in the same tertiary referral center. RESULTS: NF-PitNET with high FSH expression had decreased immunohistochemical staining for membranous E-cadherin (p<0.0001) and increased staining for nuclear E-cadherin (p<0.0001). Furthermore, high FSH expression was associated with increased ERα staining (p=0.0002) and ERα mRNA (p=0.0039). Circulating levels of P-FSH correlated with FSH staining in NF-PitNET (p=0.0025). 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.