title: Indoleamine 2,3 dioxygenase as a prognostic and follow-up marker in melanoma. A comparative study with LDH and S100B.
abstract: BACKGROUND
  To date, lactate dehydrogenase (LDH) and S100B remain the most useful biomarkers for follow-up of melanoma patients. In recent years, indoleamine 2,3-dioxygenase (IDO), an immunosuppressive enzyme, has been proposed as a new potential tumour biomarker for melanoma. However, further studies are needed to confirm the usefulness of IDO expression as an independent prognostic factor.
  
  
  OBJECTIVE
  To explore the potential association between serum IDO levels and melanoma stage at diagnosis and recurrence, and to compare the results to those obtained with LDH and S100B. In addition, we also investigated a possible cut off for IDO level as a prognostic factor for overall survival.
  
  
  METHODS
  IDO, LDH and S100B levels were measured in serum samples of 186 patients in all melanoma stages at diagnosis and twice a year thereafter. A cut-off point for IDO levels was calculated using receiver operating characteristic curves to explore the association between these levels and the likelihood of lymphatic spread. Survival curves were estimated for patient groups stratified by IDO level (higher or lower than the cut off), using the Kaplan-Meier method.
  
  
  RESULTS
  At diagnosis, serum IDO levels were significantly higher in stages IB, II, III and IV, whereas S100B levels were significantly higher in stages III and IV, and LDH levels were only higher in stage IV. In relapsed patients, significant increases were found in levels of all three markers. Finally, overall survival was significantly longer in patients with IDO levels below a cut off of 1.65 μM at diagnosis than in those with higher levels (91.3 vs. 71.0% at 36 months).
  
  
  CONCLUSIONS
  In melanoma patients, serum IDO levels are significantly associated with disease stage, relapses and overall survival. These results indicate IDO could be a useful serum prognostic marker for melanoma.
authors.affiliation: Cruces University Hospital, Osakidetza, Biscay, Spain.
authors.forename: M V
authors.initials: MV
authors.lastname: de Lecea
authors.affiliation: University of the Basque Country UPV/EHU, Biscay, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Palomares
authors.affiliation: Burgos University Hospital, Burgos, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Al Kassam
authors.affiliation: Burgos University Hospital, Burgos, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cavia
authors.affiliation: Guy's and St. Thomas' Hospital, London, UK.
authors.forename: J L C
authors.initials: JLC
authors.lastname: Geh
authors.affiliation: Burgos University Hospital, Burgos, Spain.
authors.forename: P
authors.initials: P
authors.lastname: de Llano
authors.affiliation: Burgos University Hospital, Burgos, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Muñiz
authors.affiliation: Burgos University Hospital, Burgos, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Armesto
authors.affiliation: Cruces University Hospital, Osakidetza, Biscay, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Martinez-Indart
authors.affiliation: University of the Basque Country UPV/EHU, Biscay, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Alonso-Varona
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis / Q000556:secondary*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D012878:Skin Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D007770:L-Lactate Dehydrogenase