title: GDF-15: a novel serum marker for metastases in uveal melanoma patients.
abstract: BACKGROUND
  About 50% of patients with uveal melanoma (UM) develop metastases during the course of their disease. We analyzed serum levels of Growth Differentiation Factor-15 (GDF-15), with the aim of identifying patients with early metastases.
  
  
  METHODS
  GDF-15 concentration was measured using an enzyme-linked immunosorbent assay (ELISA) in serum samples from 188 UM patients (170 patients without metastases; 18 patients with clinically detectable metastases) and 18 healthy control individuals. Data were analyzed with respect to differences between patients with and without clinically detectable UM metastases. GDF-15 serum levels were further analyzed with regard to significant patient and tumor characteristics as revealed by histology and multiplex ligation-dependent probe amplification (MLPA) to determine chromosome 3 copy number. GDF-15 expression in UM was investigated by immunohistochemistry.
  
  
  RESULTS
  Patients with clinically detectable metastases had significantly higher GDF-15 serum levels compared to those without clinically detectable metastases as well as to healthy individuals (ANOVA; p < 0.001). GDF-15 concentrations in UM patients with overt clinically detectable metastases were significantly higher than those in UM patients with a second malignancy in remission but without clinically detected UM metastases (ANOVA; p < 0.001). No association between serum concentration of GDF-15 and clinical, pathological, and genetic features was observed. GDF-15 protein was only expressed in a minority of UM cells in most tumors.
  
  
  CONCLUSIONS
  Our data suggest that GDF-15 can be used as a serum marker for the diagnosis of metastases in UM patients. Further data collection and analysis are necessary to evaluate a possible prognostic role of GDF-15 in predicting early metastases.
authors: Department of Ophthalmology, Eberhard-Karls University Tuebingen, Schleichstr. 12-16, 72076 Tuebingen, Germany. daniela.suesskind@med.uni-tuebingen.de
authors: Daniela
authors: D
authors: Suesskind
authors: Andreas
authors: A
authors: Schatz
authors: Sven
authors: S
authors: Schnichels
authors: Sarah E
authors: SE
authors: Coupland
authors: Sarah L
authors: SL
authors: Lake
authors: Bernd
authors: B
authors: Wissinger
authors: Karl U
authors: KU
authors: Bartz-Schmidt
authors: Sigrid
authors: S
authors: Henke-Fahle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005784:Gene Amplification; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008113:Liver Neoplasms; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000556:secondary; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D011446:Prospective Studies; D014604:Uveal Neoplasms / Q000097:blood* / Q000473:pathology
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D007770:L-Lactate Dehydrogenase