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Basic Science
Expression and Clinical Role of Growth Differentiation Factor-15 in Ovarian Carcinoma Effusions
  1. Annika J. Bock, BSc*,†,
  2. Helene T. Stavnes, BSc*,
  3. Tibor Kempf, MD‡,
  4. Claes G. Tropè, MD, PhD§∥,
  5. Aasmund Berner, MD, PhD*,∥,
  6. Ben Davidson, MD, PhD*,∥ and
  7. Anne Cathrine Staff, MD, PhD†∥
  1. * Division of Pathology, Oslo University Hospital, Norwegian Radium Hospital;
  2. † Department of Obstetrics and Department of Gynecology, Oslo University Hospital, Ullevål, Oslo, Norway;
  3. ‡ Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany;
  4. § Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital; and
  5. ∥ The Medical Faculty, University of Oslo, Oslo, Norway.
  1. Address correspondence and reprint requests to Ben Davidson, MD, PhD, Division of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. E-mail: bend{at}medisin.uio.no.

Abstract

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.

  • GDF-15
  • Ovarian carcinoma
  • Effusions
  • Survival

http://dx.doi.org/10.1111/IGC.0b013e3181f7d6be

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