GDF-15: a novel serum marker for metastases in uveal melanoma patients

Graefes Arch Clin Exp Ophthalmol. 2012 Jun;250(6):887-95. doi: 10.1007/s00417-011-1786-6. Epub 2011 Sep 1.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood*
  • Chromosomes, Human, Pair 3 / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Amplification
  • Growth Differentiation Factor 15 / blood*
  • Humans
  • Immunohistochemistry
  • L-Lactate Dehydrogenase / blood
  • Liver Neoplasms
  • Male
  • Melanoma / blood*
  • Melanoma / secondary
  • Middle Aged
  • Multiplex Polymerase Chain Reaction
  • Prospective Studies
  • Uveal Neoplasms / blood*
  • Uveal Neoplasms / pathology

Substances

  • Biomarkers
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • L-Lactate Dehydrogenase