title: Expression and clinical role of growth differentiation factor-15 in ovarian carcinoma effusions.
abstract: BACKGROUND
  Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β family. We analyzed the expression and clinical role of GDF-15 in ovarian carcinoma effusions.
  
  
  METHODS
  The concentration of soluble GDF-15 was measured in 195 effusion supernatants from 162 patients with ovarian carcinoma by an immunoradiometric assay. Tumor cell GDF-15 expression was investigated in 114 effusions from the same patients using immunohistochemistry.
  
  
  RESULTS
  Growth differentiation factor-15 was detected in all effusion supernatants by immunoradiometric assay. Growth differentiation factor-15 cytoplasmic expression in carcinoma cells was seen in 111 (97%) of 114 specimens. Effusion GDF-15 concentration correlated positively with GDF-15 tumor cell expression (P < 0.001). Growth differentiation factor-15 concentration was higher in effusions from patients who previously received chemotherapy compared with specimens from patients not treated with chemotherapy (P = 0.028). High GDF-15 effusion concentration was associated with poor response to chemotherapy at first disease recurrence (P = 0.001). In univariate survival analysis, high concentration of GDF-15 in effusions was associated with poor overall survival (P = 0.016), and this finding retained its prognostic value in Cox multivariate analysis (P = 0.01). Tumor cell expression of GDF-15 did not correlate with survival in analysis of the entire cohort. However, high tumor cell GDF-15 expression in prechemotherapy specimens was associated with poor progression-free survival (P = 0.046).
  
  
  CONCLUSIONS
  Soluble GDF-15 is universally present in effusions from patients with ovarian carcinoma, and tumor cells represent a likely source for soluble GDF-15 in effusions. Growth differentiation factor-15 emerges as a potential prognostic biomarker in ovarian carcinoma.
authors.affiliation: Division of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Annika J
authors.initials: AJ
authors.lastname: Bock
authors.forename: Helene T
authors.initials: HT
authors.lastname: Stavnes
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropè
authors.forename: Aasmund
authors.initials: A
authors.lastname: Berner
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.forename: Anne Cathrine
authors.initials: AC
authors.lastname: Staff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000378:metabolism; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D055436:Growth Differentiation Factor 15 / Q000097:blood / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009994:Osmolar Concentration; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D055436:Growth Differentiation Factor 15