title: KISS1 receptor is preferentially expressed in clinically non-functioning pituitary tumors.
abstract: OBJECTIVE
  KISS1 is a metastasis suppressor gene involved in cancer biology. Given the high expression levels of KISS1 and KISS1R in the hypothalamus and the pituitary respectively, we hypothesized that this system could possibly affect tumor invasiveness and clinical behavior of pituitary tumors.
  
  
  METHODS
  Expression levels of KISS1 and KISS1R mRNA were evaluated by RT-PCR. Clinical information pertaining tumor characteristics was extracted from patients' charts.
  
  
  RESULTS
  Tumors from 39 patients (21 females, mean age 47.5 years) were examined. KISS1R was expressed in 26 (67%) of samples (94% of NFPA, 42% of GH-, 67% of ACTH-, and 25% of PRL-secreting adenomas) and was found more often in female patients (81 vs. 50% males, p < 0.05); and in NFPA (94 vs. 45.5% in secreting tumors; p = 0.003). Patients expressing KISS1R were older at presentation (50.5 ± 1.4 vs. 38.1 ± 1.3 years; p = 0.008). In the multivariate analysis, factors significantly associated with KISS1R expression included female gender (OR 13.8, 95 % CI 1.22-155.9; p = 0.03) and having a NFPA (OR 24.7, 95% CI 1.50-406.4; p = 0.02). Tumor size, invasiveness and age at presentation were not independently associated with KISS1R expression. Pituitary tumors and normal pituitary were negative for KISS1 mRNA expression.
  
  
  CONCLUSIONS
  The majority of human NFPA expressed KISS1R with lower rates of expression in other types of pituitary tumors. KISS1R expression did not impart a clinical beneficial tumor phenotype, as it was not associated with tumor size or invasiveness. Additional studies are required to elucidate the role of KISS1 receptor in pituitary gland physiology and pathology.
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 64239, Tel Aviv, Israel.
authors.forename: Marianna
authors.initials: M
authors.lastname: Yaron
authors.forename: Ulrich
authors.initials: U
authors.lastname: Renner
authors.forename: Suzan
authors.initials: S
authors.lastname: Gilad
authors.forename: Günter K
authors.initials: GK
authors.lastname: Stalla
authors.forename: Naftali
authors.initials: N
authors.lastname: Stern
authors.forename: Yona
authors.initials: Y
authors.lastname: Greenman
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D059648:Kisspeptins / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D015175:Prolactinoma / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D000074502:Receptors, Kisspeptin-1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1