title: Long-term significance of urinary neopterin in ovarian cancer: a study by the Austrian Association for Gynecologic Oncology (AGO).
abstract: Neopterin is produced by activated macrophages upon stimulation with interferon-γ (IFN-γ) and thus, elevated neopterin concentrations in patients indicate cellular inate immune response. Most studies in patients with malignant diseases found an association between higher neopterin concentrations and reduced survival and impaired prognosis. Nevertheless, neopterin is not a classical tumor marker since it is not produced by the cancer cells themselves.
  
  
  
  In a study conducted by the Austrian Gynecologic Oncology Group (AGO) in 114 patients with ovarian cystadenomas and 223 patients with invasive ovarian cancer, patients' urinary neopterin was determined before and after primary therapy. The relevance of neopterin in long-term median follow-up was assessed.
  
  
  
  Elevated levels (cut-off 250 µmol/mol creatinine) were found less frequently in women with benign ovarian cystadenomas (24%) than in patients with malignant disease (58%). After 10 years, only 57% of ovarian cancer patients with elevated urinary neopterin levels survived without disease progression following primary therapy when compared with 86% of women with normal levels (P < 0.001). Along with residual tumor, FIGO stage, age and histological type, neopterin was significantly associated with overall survival (OS) and progression-free survival (PFS). The median PFS was 52 and 12 months and the median OS was 81 and 24 months for patients with normal and elevated neopterin, respectively, P < 0.001. In a multivariate Cox regression analysis, only residual tumor, neopterin and age were independently associated with OS, while only residual tumor was predictive for PFS. Thirty patients with early-stage invasive ovarian cancer (FIGO I and II) were analyzed separately. Of 3 patients with elevated neopterin, 2 died of disease in contrast to 2 out of 27 patients with normal neopterin (P = 0.004).
  
  
  
  In ovarian cancer, the negative impact of elevated urinary neopterin levels indicates a detrimental effect of cancer-associated inflammatory reaction.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Innsbruck, Innsbruck.
authors.forename: B M
authors.initials: BM
authors.lastname: Volgger
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Innsbruck, Innsbruck.
authors.forename: G H
authors.initials: GH
authors.lastname: Windbichler
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Innsbruck, Innsbruck.
authors.forename: A G
authors.initials: AG
authors.lastname: Zeimet
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Salzburg, Salzburg.
authors.forename: A H
authors.initials: AH
authors.lastname: Graf
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Salzburg, Salzburg.
authors.forename: G
authors.initials: G
authors.lastname: Bogner
authors.affiliation: Department of Obstetrics and Gynecology, Barmherzige Schwestern Linz, Linz.
authors.forename: L
authors.initials: L
authors.lastname: Angleitner-Boubenizek
authors.affiliation: Department of Obstetrics and Gynecology, Hospital Bregenz, Bregenz.
authors.forename: M
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Department of Obstetrics and Gynecology, Wilhelminenspital, Vienna.
authors.forename: U
authors.initials: U
authors.lastname: Denison
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Vienna, Vienna.
authors.forename: G
authors.initials: G
authors.lastname: Sliutz
authors.affiliation: Department of Obstetrics and Gynecology, Eisenstadt General Hospital, Eisenstadt.
authors.forename: L C
authors.initials: LC
authors.lastname: Fuith
authors.affiliation: Division of Biological Chemistry, Biocenter, Medical University, Innsbruck, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Innsbruck, Innsbruck christian.marth@tirol-kliniken.at.
authors.forename: C
authors.initials: C
authors.lastname: Marth
mesh_terms: D000328:Adult; D000368:Aged; D001317:Austria; D014408:Biomarkers, Tumor / Q000652:urine*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000652:urine; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000473:pathology / Q000652:urine; D019798:Neopterin / Q000652:urine*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D019798:Neopterin; D007371:Interferon-gamma
keywords: immunity; inflammation; neopterin; ovarian cancer; prognosis; tumor marker