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

J Clin Endocrinol Metab. 2020 Aug 1;105(8):2587-2594. 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.

Keywords: E-cadherin; FSH; PitNET; pituitary adenoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / analysis
  • Antigens, CD / metabolism*
  • Cadherins / analysis
  • Cadherins / metabolism*
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Epithelial-Mesenchymal Transition*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Follicle Stimulating Hormone / analysis
  • Follicle Stimulating Hormone / metabolism*
  • Gonadotrophs / cytology
  • Gonadotrophs / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Pituitary Neoplasms / blood
  • Pituitary Neoplasms / pathology*
  • Retrospective Studies

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Follicle Stimulating Hormone