Expression and clinical role of growth differentiation factor-15 in ovarian carcinoma effusions

Int J Gynecol Cancer. 2010 Dec;20(9):1448-55. doi: 10.1111/IGC.0b013e3181f7d6be.


Introduction: 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Ascitic Fluid / metabolism*
  • Ascitic Fluid / pathology
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • Carcinoma / blood
  • Carcinoma / diagnosis
  • Carcinoma / mortality
  • Carcinoma / pathology*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Growth Differentiation Factor 15 / blood
  • Growth Differentiation Factor 15 / metabolism*
  • Growth Differentiation Factor 15 / physiology*
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Osmolar Concentration
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Predictive Value of Tests
  • Prognosis
  • Survival Analysis


  • Biomarkers, Tumor
  • Growth Differentiation Factor 15